beta-endorphin and Pain

The Bonny Method of Guided Imagery and Music (GIM) is a music-centered approach to exploring consciousness for personal growth and transformation. Applications have been reported in a variety of clinical and nonclinical contexts.. The purpose of this study was to review evidence that a series of Bonny Method of GIM sessions may promote positive health outcomes in adults.. This systematic review examined randomized and nonrandomized controlled trials and repeated measures designs that reported psychological or physiological outcomes following a series of at least six individual Bonny Method of GIM sessions. Researchers assessed each study for risk of bias and computed effect sizes for outcome variables.. Of 270 non-duplicate titles retrieved, nine met criteria for inclusion, and eight had moderate or low risk of bias. These included 275 participants 18-78 years of age representing a variety of populations. Multiple studies measured anxiety, depression, mood disturbance, interpersonal problems, quality of life, sense of coherence, and/or psychiatric symptoms and found medium to large effect sizes. Four included physiological measures (systolic and diastolic blood pressure, beta-endorphin, cortisol, and pain) and reported medium to large effect sizes, none of which were replicated across studies in this review.. Evidence is promising that a series of Bonny Method of GIM sessions may be effective for improving both psychological and physiological health and may be therapeutically indicated for adults seeking treatment with medical, mental health, and nonclinical needs. Further research is needed to replicate findings within outcomes and populations.

Topics: Anxiety; beta-Endorphin; Bias; Blood Pressure; Controlled Clinical Trials as Topic; Depression; Humans; Hydrocortisone; Imagery, Psychotherapy; Mental Health; Mood Disorders; Music; Music Therapy; Pain; Quality of Life; Treatment Outcome

An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain. It is reported that this receptor has a functional role in controlling blood glucose levels via the modulation of insulin secretion. However, its physiological function in the brain remains unknown. Our previous studies have shown that GPR40/FFA1 is expressed in pro-opiomelanocortin (POMC)-positive neurons of the arcuate nucleus, serotonergic neurons in the nucleus raphe magnus, and in noradrenergic neurons in the locus coeruleus. Furthermore, the intracerebroventricular injection of DHA or GW9508, which is a selective GPR40/FFA1 agonist, attenuates formalin-induced inflammatory pain behavior through increasing β-endorphin release in the hypothalamus. It also suppresses complete Freund's adjuvant-induced mechanical allodynia and thermal hyperalgesia. Our findings suggest that brain free long-chain fatty acids-GPR40/FFA1 signaling might have an important role in the modulation of endogenous pain control systems. In this review, I discuss the current status and our recent study regarding a new pain regulatory system via the brain long chain fatty acid receptor GPR40/FFA1 signal.

Topics: Animals; beta-Endorphin; Blood Glucose; Brain; Docosahexaenoic Acids; Humans; Insulin; Insulin Secretion; Neurons; Pain; Receptors, G-Protein-Coupled; Signal Transduction

This study aimed to review research on the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on β-endorphin. NSAIDs are commonly used as anti-inflammatory and analgesic drugs. They are well known for inducing peripheral analgesia by inhibiting cyclooxygenase (COX). However, an increasing number of studies have shown that NSAIDs have an analgesic effect not only in the periphery but also at the center. It means that a central analgesic mechanism of the action of NSAIDs exists besides the peripheral mechanism, and the central mechanism likely involves β-endorphin. β-Endorphin is one of the most prominent endogenous peptides, existing in the hypophysis cerebri and hypothalamus. It plays an irreplaceable role in the central and peripheral analgesia in the human body mainly through three mechanisms including three parts, the spinal cord, the supraspinal cord, and peripheries. β-Endorphin plays an important role in the development of hyperalgesia. However, the specific signal transduction pathways between prostaglandin E

Topics: Analgesia; Anti-Inflammatory Agents, Non-Steroidal; beta-Endorphin; Cyclooxygenase Inhibitors; Dinoprostone; Humans; Hyperalgesia; Pain; Prostaglandin-Endoperoxide Synthases; Signal Transduction

Beta-endorphin (β-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how β-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of β-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.

Topics: Animals; Behavior; Behavior, Animal; beta-Endorphin; Cell Communication; Central Nervous System; Eating; Extracellular Space; Humans; Motivation; Pain; Reward; Sexual Behavior

Fatty acids, one class of essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a variety of biological phenomena. The important functional role of fatty acids in both onset and suppression of pain has become increasingly apparent in recent years. Recently, we have also demonstrated that the release of an endogenous opioid peptide, β-endorphin, plays an important role in the induction of docosahexaenoic acid (DHA)-induced antinociception. It is well known that fatty acids affect intracellular and intercellular signaling as well as the membrane fluidity of neurons. In addition to intracellular actions, unbound free fatty acids (FFAs) can also carry out extracellular signaling by stimulating the G protein-coupled receptor (GPCR). Among these receptors, G protein-coupled receptor 40 (GPR40) has been reported to be activated by long-chain fatty acids such as DHA, eicosapentaenoic acid (EPA) and arachidonic acid. In the peripheral area, GPR40 is preferentially expressed in pancreatic β-cells and is known to relate to the secretion of hormone and peptides. On the other hand, even though this receptor is widely distributed in the central nervous system, reports studying the role and functions of GPR40 in the brain have not been found. In this review, we summarize the findings of our recent study about the long-chain fatty acid receptor GPR40 as a novel pain regulatory system.

Topics: Analgesics; Animals; beta-Endorphin; Docosahexaenoic Acids; Fatty Acids; Humans; Pain; Receptors, G-Protein-Coupled

It is well known that a multitude of ligands and receptors are involved in the nociceptive system, and some of them increase, while others inhibit the pain sensation both peripherally and centrally. These substances, including neurotransmitters, neuromodulators, hormones, cytokines etc., may modify the activity of nerves involved in the pain pathways. It is also well known that the organism can express very effective antinociception in different circumstances, and during such situations the levels of various endogenous ligands change. Accordingly, a very exciting field of pain research relates to the roles of endogenous ligands. The peripheral action may possibly be extremely important, because low doses of the endogenous ligands may reduce pain without disphoric side-effects, and without the abused potential typical of centrally acting ligands. This review provides a comprehensive overview of the endogenous ligands that can induce antinociception, discusses their effects on different receptors and focuses on their action at peripheral level. We found 17 different endogenous ligands which produced antinociception after their topical administration. The results suggest an important direction for the development of pain strategies that focus on the local administrations of different endogenous ligands.

Topics: Analgesics, Opioid; Animals; Annexin A1; beta-Endorphin; Cytokines; Endorphins; Excitatory Amino Acid Agents; Hemoglobins; Kynurenic Acid; Ligands; Lipid Metabolism; Melatonin; Mice; Neuropeptides; Neurotransmitter Agents; Nociceptin; Oligopeptides; Opioid Peptides; Pain; Pain Measurement; Pain Threshold; Peptide Fragments; Peripheral Nervous System; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Somatostatin

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; beta-Endorphin; Humans; Neurotransmitter Agents; Pain; Peripheral Nervous System; Pituitary Gland; Receptors, Opioid

In the present study, we demonstrated that repeated treatment with fentanyl, but not morphine or oxycodone, causes a rapid desensitization to its ability to block the hyperalgesia associated with the attenuation of mu-opioid receptor resensitization in mice in a chronic pain-like state. In contrast, no such effect was noted in beta-endorphin knockout mice under the chronic pain-like conditions. On the assumption that beta-endorphin might be released within the spinal cord under pain-like conditions, we further examined whether beta-endorphin could be responsible for a desensitization and resensitization of fentanyl under the chronic pain. In cultured cells, unlike morphine, fentanyl and oxycodone induced a robust mu-opioid receptor internalization and, in turn, its resensitization. In the presence of beta-endorphin, the internalized mu-opioid receptor induced by fentanyl, but not oxycodone, remained within the cytosolic component even after washing out. The findings suggest that beta-endorphin could attenuate the resensitization of mu-opioid receptors. This phenomenon may explain the high degree of tolerance to fentanyl that develops with hyperalgesia caused by a chronic pain-like state.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Chronic Disease; Disease Models, Animal; Drug Tolerance; Fentanyl; Humans; Mice; Morphine; Oxycodone; Pain; Receptors, Opioid, mu

The accurate assessment of pain is needed to control cancer pain and its treatment. Pain itself is subjective experience and is difficult to estimate quantitatively. Until now, there is no precise method to quantitate the cancer pain objectively. First, we show the tools to assess cancer pain by patient's description, including visual analogue scales, verval rating scales and numerical rating scales and so on. These scales have been used to evaluate the intensity of clinical pain, however they cannot assess the quality of cancer pain and only McGill Pain Questionnaire (MPQ) has specificity for the qualitative and quantitative properties of clinical pain. Molecular biological approach has been advanced in the neuroscience field to find the candidate of neuropathic pain. In this article, we would like to show the results of the proteomics research for neuropathic pain. We also tried to discuss about the biomarker and its possibility whether it can reflect cancer pain and effect of cancer treatment.

Topics: Animals; beta-Endorphin; Biomarkers; Cholecystokinin; Cytokines; Humans; Neoplasms; Oxidative Stress; Pain; Pain Measurement

It is well established that cholecystokinin (CCK) reduces the antinociceptive effect of opioids. The level of CCK and CCK receptors, as well as CKK release, exhibits considerable plasticity after nerve injury and inflammation, conditions known to be associated with chronic pain. Such altered CCK release coupled in some situation with changes in CCK receptor levels may underlie the clinical phenomenon of varying opioid sensitivity in different clinical pain conditions. In particular, neuropathic pain after injury to the peripheral and central nervous system does not respond well to opioids, which is likely to be caused by increased activity in the endogenous CCK system. CCK receptor antagonists may thus be useful as analgesics in combination with opioids to treat neuropathic pain.

Topics: Analgesia; Animals; beta-Endorphin; Cholecystokinin; Chronic Disease; Humans; Inflammation; Morphine; Pain; Rats; Receptors, Cholecystokinin; Spinal Cord Injuries

Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus and in widespread areas of the brain following exposure to stressors. It is considered to be a mediator of many of the effects of stress, and its analgesic properties have been demonstrated in many studies. However, for primarily methodological reasons, the effects of CRF in the central nervous system have been neglected whereas the peripheral effects of CRF have been overemphasized. We present evidence that: (1) CRF can act at all levels of the neuraxis to produce analgesia; (2) the release of beta-endorphin does not explain the analgesia following intravenous or intracranial CRF administration; (3) inflammation must be present for local CRF to evoke analgesia and (4) the analgesic effects of CRF show specificity for prolonged pain. These findings suggest that CRF may have a significant role in chronic pain syndromes associated with hypothalamic-pituitary-adrenal axis abnormalities. Furthermore, CRF may represent a new class of analgesics that merits further study. Implications for the relationship between stress and pain are discussed.

Topics: Analgesia; Animals; beta-Endorphin; Brain; Corticotropin-Releasing Hormone; Humans; Hypothalamus; Pain

We have known the endogenous opioid peptide beta-endorphin for 20 years. Surprisingly, our knowledge of the physiological role of this peptide and its receptors in modulation of pain perception is still fragmentary. Whereas most studies have tried to elucidate the physiological role of beta-endorphin by reversing evoked responses by the opioid antagonist naloxone, this review focuses on quantification of release of beta-endorphin in the brain as the approach to define physiological and pathophysiological roles of beta-endorphin in relation to nociception. Using a lateral ventricle-cisterna magna perfusion model in the anesthetized rat, it was shown that depolarization of neurons in the arcuate nucleus of the hypothalamus, where beta-endorphin in produced, was followed by release of beta-endorphin to the cerebrospinal fluid compartment. Intense activation of spinal nociceptive pathways by intrathecal capsaicin injections also led to beta-endorphin release. It is concluded that there may still be good reason to quantify beta-endorphin in human cerebrospinal fluid to elucidate the role of beta-endorphin in pain perception.

Topics: Animals; beta-Endorphin; Brain; Capsaicin; Electric Stimulation; Excitatory Amino Acid Agonists; Humans; N-Methylaspartate; Pain

The contrasting findings obtained in the studies that have attempted to correlate the stage of endometriosis with severity of pain symptoms suggest that some specific characteristics of the lesions are more implicated in the genesis of pain than disease extension per se. Thus, fresh, metabolically active, intraperitoneal implants may cause functional pain symptoms such as dysmenorrhea, whereas infiltrating, nodular and fibrotic lesions are responsible for organic-type pain such as deep dyspareunia. Women with symptomatic endometriosis seem to have reduced peripheral beta-endorphin production in comparison with pain patients without the disease, although neuroendocrine modulation of pelvic nociceptive stimuli is far from clear. There is little evidence to support the notion that specific psychiatric features render some women more vulnerable to developing endometriosis, as results from investigations performed on women with asymptomatic lesions are very similar to normative data. Moreover, it appears that the psychological profile of symptomatic patients with the disease is no different from those with pain and a normal pelvis or other gynecological conditions. Consequently, the local biochemical and physical effects of lesions seem to be the most important factors in determining frequency and severity of symptoms.

Topics: beta-Endorphin; Dysmenorrhea; Dyspareunia; Endometriosis; Female; Genitalia, Female; Humans; Laparotomy; Mood Disorders; Pain; Peritoneal Diseases

When an endogenous morphine, beta-endorphin was discovered ten years ago, the fact that this morphine is present in the brain and many other tissues suggested to neurobiologists that these peptide opiates play a role which goes beyond that of a simple modulator of the perception of pain. beta-endorphin is a neurohormone which is secreted by the pituitary gland and reaches all tissues present in the body by diffusion. Many laboratories have investigated variations in serum levels of beta-endorphin under widely varying physiological or pathological conditions. Many references to these studies in the literature have thus demonstrated that beta-endorphins play a role in certain behavioural patterns (stress, alcoholism), in obesity, diabetes and psychiatric diseases. In fact, the activity of beta-endorphins would appear to have an interesting role to play and are a promising feature in the treatment of cerebral aging; in this field, beta-endorphins act not only as neuroregulators of other neurotransmitting substances but also, via calcium channels, exert an effect on the walls of cerebral arterioles. In situ, the role of beta-endorphins at the ionic channel level has been studied using the patch-clamp technique. In 1991, E Neher and B Sakmann received the Nobel Medicine and Physiology Prize for this work. beta-endorphin, which may be the "missing link" between the neuron and the wall of the arteriole, must be considered as being a fundamental neurotransmitter in the same way as well-known substances such as noradrenaline, acetylcholine, serotonin, dopamine and the GABAergic system are also neurotransmitters.

Topics: Behavior; beta-Endorphin; Humans; Ion Channels; Neurotransmitter Agents; Pain

Topics: Animals; Antibodies; beta-Endorphin; Disease Models, Animal; Endorphins; Immunity, Cellular; Inflammation; Naloxone; Neuroimmunomodulation; Neurons, Afferent; Pain; Pain Threshold; Rats; Receptors, Opioid

Topics: Amino Acid Sequence; Animals; beta-Endorphin; Endorphins; Humans; Molecular Sequence Data; Pain; Receptors, Opioid; Sequence Homology, Amino Acid; Stress, Physiological

Topics: Acupuncture Analgesia; Analgesics; beta-Endorphin; Combined Modality Therapy; Humans; Nociceptors; Pain; Pain Management; Receptors, Opioid; Stimulation, Chemical

The most important studies on weather-related pain have been analysed and their results compared. Since different medicometeorological classifications were used, and individual reactions to the weather vary considerably, it is possible to recognize unequivocal, universally valid relationships only with difficulty. Rheumatic pain arises mainly in a cold front area, in unstable polar air, and in thunderstorms. Amputation- and scar-related pain is similarly dependent upon changes in the weather. Headaches and migraine are typical signs of an imminent change in the weather. The question as to whether or not the endorphin concentration is of significance for meteorogenic pain is discussed, and possible influences of atmospherics activity noted.

Topics: beta-Endorphin; Humans; Nociceptors; Pain; Pain Measurement; Sensory Thresholds; Weather

Topics: Adolescent; Adolescent Behavior; Bandages; beta-Endorphin; Burns; Child; Child Behavior; Child, Hospitalized; Child, Preschool; Clinical Protocols; Depression; Humans; Hydrocortisone; Infant; Narcotics; Pain; Reproducibility of Results

Topics: beta-Endorphin; Coronary Disease; Enkephalins; Humans; Pain; Perception; Pressoreceptors; Receptors, Opioid; Sensory Thresholds

The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.

Topics: Aging; Animals; Arousal; beta-Endorphin; Brain; Catecholamines; Hemodynamics; Ischemia; Neuropeptide Y; Pain; Rats; Rats, Inbred SHR; Receptors, Adrenergic, alpha; Receptors, Glucocorticoid; Synapses; Synaptic Membranes; Synaptic Transmission

Topics: Animals; beta-Endorphin; Brain; Endorphins; Enkephalins; Humans; Pain; Rats; Receptors, Opioid; Spinal Cord; Substance P

Topics: Animals; beta-Endorphin; Gonadal Steroid Hormones; Humans; Hypothalamo-Hypophyseal System; Pain; Stress, Physiological

Topics: beta-Endorphin; Coronary Disease; Diagnosis, Differential; Humans; Male; Middle Aged; Pain; Pain Measurement

Evidence suggests that endogenous opioids, particularly the beta-endorphins and met-enkephalins, are closely involved in stress-induced analgesia and nociceptive pain control. Numerous investigations have been conducted to evaluate the role of opioids in silent vs symptomatic myocardial disease. There is good evidence to suggest that patients with asymptomatic ischemia have defective pain perception compared with those with angina; however, the precise role of the endorphin and enkephalin systems in this phenomenon remains to be elucidated. Possible sources for disparate study results include variation in patient populations, insensitive or improperly timed assay techniques, and differences in amount of ischemia.

Topics: Angina Pectoris; beta-Endorphin; Coronary Disease; Endorphins; Exercise Test; Humans; Pain

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arthritis; Arthritis, Experimental; Benzomorphans; beta-Endorphin; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Morphine; Naloxone; Nociceptors; Pain; Pituitary Gland, Anterior; Protein Precursors; Pyrrolidines; Rats; Receptors, Opioid; Sensory Thresholds; Spinal Cord; Thalamus

Topics: Analgesia; Animals; beta-Endorphin; Brain; Electric Stimulation; Endorphins; Enkephalins; Male; Pain; Pro-Opiomelanocortin; Protein Precursors; Rats; Sensory Thresholds; Stress, Physiological; Time Factors

Topics: Acupuncture Therapy; Animals; beta-Endorphin; Blood-Brain Barrier; Cats; Circadian Rhythm; Copulation; Electrophysiology; Endorphins; Hot Temperature; Hypophysectomy; Naloxone; Narcotics; Pain; Physical Exertion; Sexual Behavior, Animal; Stress, Physiological

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; beta-Endorphin; Circadian Rhythm; Dynorphins; Endocrine Glands; Endorphins; Enkephalins; Female; Humans; Hypothalamo-Hypophyseal System; Islets of Langerhans; Melanocyte-Stimulating Hormones; Oxytocin; Pain; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Pregnancy; Rats; Receptors, Opioid; Shock; Stress, Physiological

Topics: Animals; beta-Endorphin; Brain; Endorphins; Enkephalins; Humans; Pain; Protein Precursors; Receptors, Opioid

Vigorous exercise is associated with a sensation of well-being, and this subjective state has been objectively quantified with psychometric, cardiovascular, and neurophysiological data. Reductions in state anxiety have been demonstrated to follow acute physical activity, and this response persists for 2-5 h. Chronic physical activity has been associated with reductions in anxiety and depression, as well as increases in self-esteem. This research has been limited to designs of a correlational nature, and the issue of causality vs mere association has not been resolved or addressed. Three hypotheses based upon distraction, monoamine metabolism, and endorphin release are discussed in this paper. Investigators have traditionally attempted to illustrate the mechanism involved in improved mood following exercise by testing one of these or related hypotheses, but it is likely that advances will not be made in this area until these hypotheses are examined in a multiple or synergistic manner. It is concluded that each of the hypotheses reviewed remains tenable.

Topics: Affect; Animals; Anxiety; beta-Endorphin; beta-Lipotropin; Endorphins; Euphoria; Female; Humans; Male; Norepinephrine; Pain; Physical Exertion; Rats; Running; Sensory Thresholds; Serotonin; Stress, Psychological

Topics: Acetylcholine; Afferent Pathways; Analgesics; Animals; beta-Endorphin; Brain Stem; Dynorphins; Endorphins; Enkephalins; Medulla Oblongata; Models, Biological; Neural Pathways; Neurons; Neurotensin; Norepinephrine; Pain; Peptide Fragments; Periaqueductal Gray; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors; Spinal Cord; Stress, Physiological

This article provides a broad overview of current thinking about pain and then outlines an approach to a unique category of pain, recurrent pains of obscure origin.

Topics: Attitude to Health; beta-Endorphin; Child; Child Development; Diagnostic Tests, Routine; Endorphins; Enkephalins; Ethnicity; Family; Female; Humans; Male; Medical History Taking; Neurotransmitter Agents; Nociceptors; Pain; Pain Management; Personality; Physical Examination; Psychology, Child; Recurrence; Sensation; Sensory Thresholds; Sex Factors; Synaptic Transmission

Topics: Action Potentials; Acupuncture Therapy; Analgesia; Anesthesia, Dental; Animals; beta-Endorphin; Cats; Endorphins; Humans; Medicine, Chinese Traditional; Mice; Nerve Block; Pain; Rabbits; Rats; Trigeminal Nucleus, Spinal

Topics: Adrenocorticotropic Hormone; Analgesia; Animals; Behavior; beta-Endorphin; beta-Lipotropin; Brain; Chemical Phenomena; Chemistry; Endorphins; Enkephalins; Growth Hormone; Humans; Hydrocortisone; Neurotransmitter Agents; Pain; Pituitary Hormones; Prolactin; Rats; Thyrotropin

Topics: Adult; Aged; beta-Endorphin; Chronic Disease; Depressive Disorder; Dexamethasone; Endorphins; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pain; Pituitary Hormones, Anterior; Pituitary-Adrenal System

Topics: Animals; beta-Endorphin; Cardiovascular System; Central Nervous System; Digestive System; Endocrine Glands; Endorphins; Enkephalins; Humans; Mental Disorders; Pain

Topics: Adrenocorticotropic Hormone; Amino Acid Sequence; Animals; Base Sequence; beta-Endorphin; beta-Lipotropin; Codon; Endorphins; Genes; Humans; Hypothalamus; Melanocyte-Stimulating Hormones; Pain; Pituitary Gland; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors; Protein Processing, Post-Translational

Topics: Affective Disorders, Psychotic; Animals; Anxiety; beta-Endorphin; Catatonia; Dyskinesia, Drug-Induced; Electroconvulsive Therapy; Endorphins; Humans; Mental Disorders; Narcotic Antagonists; Opioid-Related Disorders; Pain; Rats; Receptors, Opioid; Renal Dialysis; Schizophrenia; Stress, Psychological

Topics: Animals; Anura; beta-Endorphin; Bradykinin; Cats; Central Nervous System; Endorphins; Pain; Peptides; Rats; Spinal Cord; Substance P; Synaptic Transmission; Trigeminal Nuclei

This study evaluates the effects of "laughter yoga" on the plasma beta-endorphin levels, pain levels and sleep quality of hemodialysis patients. It is a randomized controlled trial. The study was carried out between July and October 2018. A total of 68 patients receiving hemodialysis treatment at two different dialysis centers were included in the study. The duration of the laughter yoga was 30 min, and a total of 16 sessions were performed on a twice-weekly basis. The data were collected by using a socio-demographic information form, the Visual Analog Scale and the Pittsburgh Sleep Quality Index, and blood samples were collected to determine beta-endorphin levels. Following the laughter yoga implementation, the pain level of the intervention group patients significantly decreased, and their sleep quality significantly improved. No significant change occurred in the patients' beta-endorphin levels. Laughter yoga was effective in reducing pain and increasing sleep quality.

Topics: beta-Endorphin; Humans; Laughter Therapy; Pain; Quality of Life; Renal Dialysis; Sleep; Yoga

To observe the clinical efficacy and safety of electroacupuncture (EA) at Neimadian-point for cancer pain.. A total of 140 cancer patients with pain were randomly divided into EA and control groups, with 70 cases in each group. The patients of the EA group received EA at Neimadian-point plus analgesia pump (all prepared with normal saline). The patients of the control group were treated by Sufentanil patient-controlled intravenous analgesia plus sham EA (without stimulation). The treatment was conducted once daily for two days at 8 o'clock every morning. Respectively, in 1 h before treatment (T0), 1 h (T1), 8 h (T2), 24 h (T3) after treatment of the first day, 1 h (T4), 8 h (T5), 24 h (T6) after treatment of the second day, the visual analogue scale (VAS) score of pain, and the plasma levels of norepinephrine, 5-HT, leucine enkephalin, β-endorphin and dynorphin A1-13 were tested. The security level (1-4 grade) was assessed during the treatment.. Compared with their own pre-treatment, in T1 to T6, the VAS scores, and the contents of plasma norepinephrine and 5-HT obviously decreased in both groups （. EA at Neimadian-point can effectively relieve the pain of cancer patients and improve their quality of daily life.

Topics: beta-Endorphin; Cancer Pain; Electroacupuncture; Humans; Neoplasms; Pain; Pain Management

To determine the levels of two sensory neuropeptides (substance P [SP] and calcitonin gene-related peptide [CGRP]) and two endogenous opioids (methionine-enkephalin [Met-Enk] and β-endorphin [β-End]) in dental pulp tissue samples subjected to controlled orthodontic intrusive forces.. Sixteen healthy premolars were selected from eight patients who were undergoing extraction for orthodontic purposes. Eight were randomly used as controls, and the other eight were assigned to an experimental group (controlled orthodontic intrusive forces applied for 24 hours). After this period, teeth were extracted, and pulp samples were obtained. All samples were processed to quantify the expression levels of SP, CGRP, Met-Enk, and β-End using commercial radioimmunoassay kits.. All samples exhibited basal levels of both neuropeptides and endogenous opioids. After 24 hours of the intrusive stimulus, all patients reported a tolerable discomfort localized at the involved premolar. Only SP was significantly increased (P<.05). For the other molecules, no statistically significant differences were observed (P>.05); however, they expressed important increasing trends.. The expression levels of SP and CGRP in dental pulp samples from the experimental group support the positive correlation between the symptomatic clinical scenario and increased expression levels of neuropeptides, clarifying the role of neurogenic inflammation in early injury response.

Topics: Adolescent; beta-Endorphin; Bicuspid; Calcitonin Gene-Related Peptide; Child; Dental Pulp; Enkephalin, Methionine; Female; Humans; Male; Neurogenic Inflammation; Neurotransmitter Agents; Opioid Peptides; Pain; Pilot Projects; Substance P; Tooth Movement Techniques

After birth, piglets undergo procedures likely to cause stress. The aim of this study was to evaluate stress responses evoked by 2 combinations (More Stressful [all a] or Less Stressful [all a] or More Stressful [all b]) of alternative methods for performing the following processing procedures: 1) teeth resection (TR) – [a] clip vs. [b] grind; 2) identification (ID) – [a] ear tag vs. [b] ear notch; 3)iron administration (FE) – [a] inject vs. [b] oral; 4) castration (CA) – [a] cords cut vs. [b] cords torn; 5) taildocking (TD) – [a] cold clip vs. [b] hot clip [corrected]. Ten litters of eight 2- and 3-d-old piglets were assigned to each procedure. Within each litter 1 male and 1 female piglet was assigned to 1 of 4 possible procedures: the 2 combinations, sham procedures, and sham procedures plus blood sampling. Blood was collected before processing and at 45 min, 4 h, 48 h, 1 wk, and 2 wk afterward and assayed for cortisol and β-endorphin concentrations. Procedures were videotaped and analyzed to evaluate the time taken to perform the procedure and the number of squeals, grunts, and escape attempts. Vocalizations were analyzed to determine mean and peak frequencies and duration. Piglets were weighed before the procedure and at 24 h, 48 h, 1 wk, and 2 wk afterward. Identification, tail docking, and castration lesions were scored on a 0 to 5 scale at 24 h, 1 wk, and 2 wk postprocedure. Both combinations of methods took longer to carry out than sham procedures and resulted in more squeals, grunts, and escape attempts during the procedures and higher peak frequencies of vocalizations compared with the control treatments (P < 0.05). Cortisol concentrations 45 min after processing were also higher in the 2 combination treatments than in the sham treatments (P < 0.05). Comparing between procedure treatments, the More Stressful combination of methods took longer to carry out, resulted in higher β-endorphin concentrations at 1 wk, had higher peak frequency of vocalizations, and increased ear (P < 0.05) and tail wound (P < 0.1) lesion scores at 1 wk than the Less Stressful combination. Growth during d 2 to 7 postprocedure was lower in More Stressful piglets than control piglets (P < 0.05) but by 2 wk, growth was unaffected. Using measures of behavior, physiology, and productivity, the More Stressful combination of procedures decreased welfare relative to the Less Stressful combination; however, both combinations decreased welfare relative to controls. The time taken

Topics: Animal Husbandry; Animal Identification Systems; Animal Welfare; Animals; beta-Endorphin; Dentistry; Female; Hydrocortisone; Injections, Intramuscular; Iron; Male; Orchiectomy; Pain; Stress, Physiological; Swine; Tail; Tooth; Veterinary Medicine; Vocalization, Animal

To explore the effectiveness of acupuncture transcutaneous electrical nerve stimulation (Acu-TENS), a non-invasive modality in reduction of rectal discomfort during barostat-induced rectal distension.. Forty healthy subjects were randomized to receive 45 min of either Acu-TENS or placebo-TENS (no electrical output) over acupuncture points Hegu (large-intestine 4), Neiguan (pericardium 6) and Zusanli (stomach 36). A balloon catheter attached to a dual-drive barostat machine was then inserted into the subjects' rectum. A step-wise (4 mmHg) increase in balloon pressure was induced until maximal tolerable or 48 mmHg. Visual analogue scale and a 5-point subjective discomfort scale (no perception, first perception of distension, urge to defecate, discomfort/pain and extreme pain) were used to assess rectal discomfort at each distension pressure. Blood beta-endorphin levels were measured before, immediately after intervention, at 24 mmHg and at maximal tolerable distension pressure.. There was no difference in the demographic data and baseline plasma beta-endorphin levels between the two groups. Perception threshold levels were higher in the Acu-TENS group when compared to the placebo group, but the difference reached statistical significance only at the sensations "urge to defecate" and "pain". The distension pressures recorded at the "urge to defecate" sensation for the Acu-TENS and placebo-TENS groups were 28.0 ± 4.5 mmHg and 24.6 ± 5.7 mmHg, respectively (P = 0.043); and the pressures recorded for the "pain" sensation for these two groups were 36.0 ± 4.2 mmHg and 30.5 ± 4.3 mmHg respectively (P = 0.002). Compared to the placebo group, a higher number of participants in the Acu-TENS group tolerated higher distension pressures (> 40 mmHg) (65% in Acu-TENS vs 25% in placebo, P = 0.02). The plasma beta-endorphin levels of the Acu-TENS group were significantly higher than that of the placebo group at barostat inflation pressure of 24 mmHg (1.31 ± 0.40 ng/mL vs 1.04 ± 0.43 ng/mL, P = 0.044) and at maximal inflation pressure (1.46 ± 0.53 ng/mL vs 0.95 ± 0.38 ng/mL, P = 0.003).. Acu-TENS reduced rectal discomfort during barostat-induced rectal distension and concurrently associated with a rise in beta-endorphin level.

Topics: Acupuncture; Acupuncture Points; beta-Endorphin; Catheters; Dilatation; Electric Stimulation Therapy; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pain; Pain Measurement; Pressure; Rectum

To observe the effect of electroacupuncture (EA) on bispectral index (BIS) and plasma beta-endorphin (beta-EP) level in patients undergoing colonoscopy.. Sixty patients were equally randomized into EA group and control group with 30 cases in each. EA (2 Hz/100 Hz, 4-6 V) was applied to the right Zusanli (ST 36) and Shangjuxu (ST 37), and the left Yinlingquan (SP 9), Sanyinjiao (SP 6) and bilateral Hegu (LI 4) respectively 30 min before colonoscopy. The mean arterial pressure (MAP), heart rate (HR) and BIS in two groups were continuously monitored during the study. Plasma beta-EP concentration was detected by radioimmunoassay. The patient's adverse reactions (including pain, satisfaction degree, etc.) were evaluated by visual analog scale (VAS) and verbal stress scale (VSS).. Self-comparison showed that MAP and HR in control group increased significantly during colonoscope's splenic flexure passing (P<0.05). Whereas the 2 indexes in EA group had no significant changes during colonoscope insertion, and its splenic flexure passing, hepatic flexure passing and post-enteroscopy (P>0.05). Comparison between two groups showed that MAP at the time-point of colonoscope insertion, and HR at the time-point of colonoscope's splenic flexure passing in EA group were significantly lower than those in control group (P<0.05). BIS values of EA group were significantly lower than those of control group at different time-points after colonoscope insertion (P<0.01). Plasma beta-EP concentrations at the time-points of colonoscope's hepatic flexure passing and post-enteroscopy were evidently increased in both groups in comparison with pre-enteroscopy (P<0.01), and beta-EP was significantly lower in EA group than that in control group at the time-point of colonoscope's hepatic flexure passing (P<0.05). The dosage of Midazolam used for conscious-sedation and the scores of VAS and VSS were also considerably lower in EA group than those in control group (P<0.05, P<0.01). No significant differences were found between two groups in the adverse reactions as dizziness, nausea, vomiting and abdominal pain, but the patients' satisfaction degree in EA group was evidently higher than that in control group (P<0.05).. Acupuncture analgesia can effectively lower the colonoscopy patients' BIS value and plasma beta-EP level, meaning attenuation of the patients' stress responses during colonoscopy after EA.

Topics: Acupuncture Analgesia; Acupuncture Points; Adult; Aged; beta-Endorphin; Colon, Ascending; Colonoscopy; Consciousness Monitors; Electroacupuncture; Female; Humans; Male; Middle Aged; Monitoring, Intraoperative; Pain; Pain Management; Young Adult

Essential hypertension is characterised by reduced pain sensitivity. Hypertensive hypoalgesia has been attributed to elevated endogenous opioids and/or increased activation of descending pain modulation systems. A double-blind placebo-controlled design compared the effects of naltrexone and placebo on cold and ischemic pain in unmedicated newly-diagnosed patients with essential hypertension. Patients performed a cold pressor task while resting and while performing a distracting secondary task. They also performed a forearm ischemia task while resting. Although the cold pressor and ischemia tasks elicited significant increases in pain and blood pressure, pain ratings and pressor responses did not differ between naltrexone and placebo. Cold pain was reduced by distraction compared to rest. The finding that opioid blockade with naltrexone did not moderate the pain and pressor responses to cold and ischemia suggests that pain and associated blood pressure responses are not modulated by opioids in hypertension. The finding that the distracting secondary task successfully reduced pain ratings suggests normal supraspinal pain modulation in essential hypertension.

Topics: Adult; Attention; beta-Endorphin; Cold Temperature; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Myocardial Ischemia; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Touch

Although an analgesic effect is an essential component of the mode of action of bisphosphonates, its physiological mechanisms are still unclear. Beta-endorphin release plays an important role in the analgesic effect of both calcitonin and raloxifene. As patients with Paget's disease receive large doses of bisphosphonates within relatively short time periods, we examined whether repeated pamidronate infusion therapy would cause measurable change in beta-endorphin levels. Visual analog scale (VAS) scores of pain intensity, beta-endorphin levels, and alkaline phosphatase activity of 11 patients with Paget's disease (7 with the mono- and 4 with the polyostotic form) were determined at baseline, as well as after 3 and 6 infusions (on Days 6 and 12 of treatment, respectively). Eleven untreated patients with Paget's disease (7 with the mono- and 4 with the polyostotic form) served as controls.. It was established that in the course of pamidronate infusion therapy BE levels remained constant, whereas the values in serum alkaline phosphatase and pain intensity scores were significantly reduced.. Although high-dose pamidronate therapy does mitigate pain substantially (as demonstrated by the reduction of VAS scores), its analgesic action is probably unrelated to the enhancement of beta-endorphin release.

Topics: Aged; Analgesics; beta-Endorphin; Bone Density Conservation Agents; Diphosphonates; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Osteitis Deformans; Pain; Pain Measurement; Pamidronate; Pilot Projects

To explore the therapeutic effect and mechanism of Aitongping capsule (ATP) in treating cancerous pain.. Sixty cancer patients were randomly divided into two groups, 30 patients in the treated group took ATP and 30 patients in the control group took diclofenac, 1 week of treatment was applied. The relevant clinical conditions of cancerous pain, the content of plasma beta-endorphin (beta-EP) and c-AMP, hemorheological index, improuement of life quality of patients, occurrence rate of adverse reaction were observed before and after treatment.. The total effective rate in the treated group and in the control group was 90.0 % and 83.3%, respectively, difference between them showed no significance. However, there were significant difference between the two groups in such aspects as the degree of pain relieving, the decrease of pain episodes, the shortening persistent time of pain and the initiation time of analgesic action and prolonged analgesic duration, the decrease of tenderness and percussion pain, the increase of plasma beta-EP content and the decrease of cAMP (P< 0.05 or P< 0.01). The evidences also showed that it was better in improving quality of life, ameliorating hemorheologic indexes and reducing incidence of adverse reaction in the treated group than in the control group (P <0.05 or P <0.01).. ATP has affirmative effect on cancerous pain, its analgesic effect may be associated with the increasing of plasma beta-EP content, decreasing of cAMP level and ameliorating of hemorheologic indexes.

Topics: beta-Endorphin; Capsules; Cyclic AMP; Drugs, Chinese Herbal; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Pain; Phytotherapy; Quality of Life

In the present study the effects of intravenously administered corticotropin-releasing hormone (CRH) on the release of proopiomelanocortin (POMC) derivatives such as adrenocorticotropic hormone (ACTH), beta-lipotropin (beta-LPH) and beta-endorphin (beta-END) as well as direct effects of CRH on pain sensitivity were examined. In 16 healthy volunteers we studied the effects of 100 microg intravenously administered CRH in absence or presence of 12 mg naloxone on heat or pressure pain sensitivity, using a double-blind, cross-over and placebo-controlled design. To evaluate analgesic effects of CRH via release of POMC derivatives, we determined plasma concentrations of beta-END-immunoreactive material (IRM), authentic beta-END (beta-END(1-31)) and beta-LPH IRM, in parallel with heat and pressure pain tolerance thresholds before and 15 and 30 min after treatment with CRH (or placebo), and 5 min after naloxone (or placebo) administration which was administered 40 min after CRH (or placebo) injection. CRH increased levels of beta-END IRM, beta-END(1-31) and beta-LPH IRM. As compared to beta-END IRM levels measured by a commercial RIA kit, the beta-END(1-31) levels determined by a highly specific two-site RIA, proved to be remarkably small. Furthermore, CRH did not induce increases of heat pain tolerance thresholds, but of pressure pain tolerance thresholds, which, however, were not reversible by naloxone. Neither beta-END nor beta-LPH IRM nor beta-END(1-31) levels correlated with heat or pressure pain tolerance thresholds. We conclude that CRH does not modulate heat, but pressure pain; POMC derivatives like beta-END IRM, beta-END(1-31) or beta-LPH do not mediate this effect.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Cross-Sectional Studies; Female; Hot Temperature; Humans; Injections, Intravenous; Male; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Pressure

Two or three decades ago, cancer pain was treated by surgical/chemical hypophysectomy. In one report, the control of central pain (thalamic pain syndrome) was also approached with chemical hypophysectomy. Although in most of the patients these treatments resulted in a decrease in severe pain, concomitantly severe adverse effects (panhypopituitarism, diabetes insipidus and visual dysfunction) occurred in most patients. This historical evidence prompted us to perform Gamma Knife surgery (GKS) for this kind of intractable severe pain using a high irradiation dose to the pituitary stalk/gland. In the majority of patients, marked pain relief was achieved, surprisingly without any of the complications mentioned above.. A prospective multicenter study was conducted to evaluate the efficacy and safety in patients treated in Prague, Hong Kong and Tokyo. Indications of this treatment were: (1) failure of other effective treatment approaches prior to GKS, (2) good general patient condition (Karnofsky performance status >40%), (3) response to morphine for pain control (cancer pain), and (4) no previous radiotherapy of brain metastases (GKS/conventional radiotherapy). Eight patients with severe cancer pain due to bone metastasis and 12 patients with post-stroke thalamic pain syndrome were treated with GKS. The target was the border between the pituitary stalk and gland. Maximum dose was 160 Gy for cancer pain and 140 Gy for central pain. Follow-up included 6 patients (>1 month) with cancer pain and 8 patients (> 6 months) with thalamic pain syndrome.. All patients (6/6) with cancer pain experienced significant pain reduction, and 87.5% (7/8) of the patients with thalamic pain had initially significant pain reduction. In some patients, pain reduction was delayed for several hours. Pain relief was noted within 7 days (median 2 days). No recurrence was observed in the patients with cancer pain. However, in 71.4% (5/7) of the patients with thalamic pain syndrome, disease recurred during the 6-month follow-up. Up to now, other complications have not been observed.. Our clinical study protocol is only preliminary. Further clinical results on the management of thalamic pain are required to develop this treatment protocol. However, efficacy and safety have been shown in all our cases. In our opinion, this treatment has a potential to control severe pain, and GKS will play an important role in the management of intractable pain.

Topics: beta-Endorphin; Bone Neoplasms; Breast Neoplasms; Female; Humans; Hypophysectomy; Male; Pain; Pituitary Gland; Prospective Studies; Prostatic Neoplasms; Radiosurgery; Thalamus; Treatment Outcome

The purpose of the present study was to investigate whether the floating form of the restricted environmental stimulation technique (REST) may be applied within the field of pain relief. Flotation-REST consists of a procedure whereby an individual is immersed in a tank filled with water of an extremely high salt concentration. Thirty-seven patients (14 men and 23 women) suffering from chronic pain consisting of aching muscles in the neck and back area participated in the study. They were randomly assigned to either a control group (17 participants) or an experimental group (20 participants). The experimental group received nine opportunities to use the flotation-REST technique in the water tank over a three-week period. The results indicated that the most severe perceived pain intensity was significantly reduced, whereas low perceived pain intensity was not influenced by the floating technique. Further, the results indicated that circulating levels of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethyleneglycol were reduced significantly in the experimental group but not in the control group following treatment, whereas endorphin levels were not affected by flotation. Flotation-REST treatment also elevated the participants' optimism and reduced the degree of anxiety or depression; at nighttime, patients who underwent flotation fell asleep more easily. The present findings describe possible changes, for the better, in patients presenting with chronic pain complaints.

Topics: Adult; Anxiety; beta-Endorphin; Chronic Disease; Depression; Female; Headache; Humans; Male; Methoxyhydroxyphenylglycol; Muscle Contraction; Pain; Pain Management; Personality; Psychophysiologic Disorders; Relaxation Therapy; Reproducibility of Results; Sleep

The purpose of this study was to investigate whether placebo analgesia is mediated by the release of beta-endorphin. In addition to subjective pain reports, we included an objective physiological parameter of nociception reflected by the opioid sensitive nociceptive R-III reflex. Placebo consisted of strong suggestions of pain relief and an intravenous injection of saline. Forty minutes after placebo, either the opioid antagonist naloxone or saline was administered intravenously without subjects noticing (hidden). Sixty healthy males, aged 18-30 years, voluntarily participated in this study. Subjects were randomized into one of four groups: group 1 received placebo and hidden naloxone, group 2 received hidden naloxone only, group 3 received placebo and hidden saline and group 4 received hidden saline only. Pain was induced by electrical stimulation of the sural nerve and evaluated with a visual analogue scale (VAS). In addition, changes in the magnitude of the nociceptive R-III reflex activity were assessed. We determined to what extent R-III reflex activity and subjective pain reports were decreased by placebo and we investigated whether these placebo-induced changes in reflex activity and subjective pain reports were naloxone reversible. Furthermore, we measured the degree of association between pain relief as measured on VAS and changes in R-III reflex activity. Finally, the role of beta-endorphin was assessed by measuring plasma endorphin levels before and after the administration of placebo. This study could not demonstrate a placebo effect as measured on VAS and R-III responses. The administration of placebo did not appear to have an effect on the release of beta-endorphins. Consistently, the antagonizing effects of naloxone were negligible. A subgroup analysis of those who did show a placebo response as indicated on the VAS did not support the supposition that beta-endorphin is released due to placebo suggestion. It is suggested that intensified stimuli and a more effective procedure to induce placebo analgesia (e.g. conditioning) may produce a proper placebo effect.

Topics: Adolescent; Adult; beta-Endorphin; Humans; Male; Naloxone; Narcotic Antagonists; Nociceptors; Pain; Placebo Effect; Placebos; Reflex; Spinal Cord

To compare the efficacy and adverse effects of fentanyl or morphine analgesia during the first 2 days of life in newborn infants who underwent mechanical ventilation.. In a randomized double-blind trial, 163 infants were allocated to receive a continuous infusion of fentanyl (10.5 microg/kg over a 1-hour period followed by 1.5 microg/kg/hr) or morphine (140 microg/kg over a 1-hour period followed by 20 microg/kg/hr) for at least 24 hours. The severity of pain was assessed with physiological parameters, a behavioral pain scale, and stress hormone concentrations before and 2 and 24 hours after the start of treatment.. The analgesic effect was similar in both groups, as judged by the pain scale. Plasma adrenaline and noradrenaline concentrations decreased significantly from 0 to 24 hours in both groups. Median adrenaline decrease was 0.5 nmol/L (interquartile range [IQR] 1.1;0.0) in the fentanyl and 0.7 nmol/L (IQR 1.3;0.1) in the morphine group, noradrenaline 2.1 nmol/L (IQR 9.0;0.2), and 3.0 nmol/L (IQR 7. 5;0.3), respectively. beta-endorphin decreased significantly only in the fentanyl group ( 14 pmol/L (IQR 28; 7), P <.05). Decreased gastrointestinal motility was less frequent in the fentanyl group (23% vs 47%, P <.01).. With at least as effective analgesia as with morphine, fentanyl had fewer side effects. Fentanyl may be superior to morphine for short-term postnatal analgesia in newborn infants.

Topics: Analgesics, Opioid; beta-Endorphin; Catecholamines; Double-Blind Method; Fentanyl; Humans; Infant, Newborn; Morphine; Pain; Pain Measurement; Respiration, Artificial

Hyperactivity of endogenous opioid systems has been postulated to mediate the associations between defensive/repressive coping styles, enhanced stress responsivity, and reduced immunocompetence. Study 1 examined whether repressive/defensive coping would be associated with greater sensitivity to opioid antagonism. Judgments of the painfulness of ascending series of electrocutaneous stimulation applied to the forearm were determined before and after the administration of naloxone and placebo in 38 men and 42 women. All subjects were healthy with a mean age of 32.9 years. Naloxone (10 mg i.v.) and placebo were administered in double-blind fashion and counterbalanced. Subjects were classified as High- and Low-defensive and repressive copers on the basis of scores on the Marlowe-Crowne Social Desirability Scale and the Balanced Inventory of Desirable Responding, respectively. High Self-Deception was associated with naloxone-induced hyperalgesia, whereas no effects of naloxone on pain ratings were observed in low-Self-Deceptive subjects. In Study 2, resting plasma beta-endorphin levels were found to be positively correlated with defensiveness in men (n = 26), but not women (n = 44). Study 3 examined 82 healthy subjects (mean age = 28.7 years). Beta-endorphin/defensiveness correlations were found to be greater following, compared to prior to, electrical nociceptive stimulation in men (n = 49), but unrelated in women (n = 33). These findings are consistent with the hypothesized endorphinergic dysregulation associated with repressive/defensive coping styles and are discussed in terms of the immuno-regulatory implications of such a dysregulation.

Topics: Adaptation, Psychological; Adolescent; Adult; Affect; Analysis of Variance; beta-Endorphin; Defense Mechanisms; Double-Blind Method; Female; Health Status; Humans; Male; Middle Aged; Naloxone; Narcotics; Pain; Pain Measurement; Repression, Psychology; Stress, Psychological

The antinociceptive potency of corticotropin-releasing-hormone (CRH) has been established in several animal studies in which both central and peripheral sites of action were considered. However, there have not yet been any experimental trials, besides one attempt using clinical dental pain demonstrating the potential analgesic properties of CRH in humans. For this reason, we studied the effect of CRH on experimental heat pain sensitivity in 18 healthy men, using a double-blind, cross-over and placebo-controlled design. A dose of 100 microg (i.v.) was chosen because of its well-known neuroendocrine effects in humans. The pain parameters assessed were, visual analog scale (VAS) ratings for pain intensity and pain unpleasantness, pain thresholds and scores for discrimination ability. To differentiate between a direct analgesic effect of CRH and indirect effects via evoked hormonal responses in the hypothalamic-pituitary-adrenocortical (HPA) system (beta-endorphin, ACTH, cortisol), CRH was applied with and without a pre-treatment with dexamethasone. In neither of the two conditions was there any systematic change in our pain parameters. This failure to find any evidence suggesting an analgesic action of CRH or of the subsequent hormones of the HPA system was obtained despite the fact that CRH produced clear neuroendocrine responses such as increases in the plasma concentration of beta-endorphin and cortisol. It is unclear whether the lack of analgesic action of CRH is due to its non-existence in humans, due to the use of a pain model which does not assess minute changes in pain sensitivity and does not trigger substantial inflammatory responses, or due to an insufficient dose of CRH.

Topics: Adult; Analgesics; Anti-Inflammatory Agents; beta-Endorphin; Corticotropin-Releasing Hormone; Cross-Over Studies; Dexamethasone; Double-Blind Method; Evaluation Studies as Topic; Hot Temperature; Humans; Hydrocortisone; Male; Nociceptors; Pain; Pain Measurement

This prospective nonrandomized trial was performed to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain related to bone metastasis in cancer patients and the relation of sCT's analgesic efficacy with beta-endorphin blood levels. The study group consisted of 22 cancer patients with bone metastases (male 13 and female 9, age range 38-77 years). Pain control was first achieved by continuous subcutaneous (s.c.) morphine administration. The next increase in pain was managed with continuous s.c. administration of 400 IU/day sCT. Beta-endorphin blood levels were measured before and during sCT administration. The first measurement was taken before sCT administration; subsequent measurement occurred at 12, 24, and 48 hours and 7 days after the commencement of treatment. Pain scores were monitored by a visual analogue scale. A complete blood count and a biochemical screening profile were taken before the administration of calcitonin and also on the seventh and the fifteenth day of the administration. The results showed a satisfactory analgesic effect. The mean pain score before the calcitonin administration was 4.43 and the score on the seventh day was 1.17. The gradual reduction of pain score was associated with an increase in beta-endorphin blood levels (increase to 147.2% of baseline on the seventh treatment day). In three cases, no satisfactory analgesic effect was obtained and pain control was achieved by increasing the continuous s.c. morphine dosage. No significant side effects were observed. These data suggest that sCT in high doses may be a useful adjuvant analgesic when combined with low doses of morphine in continuous s.c. administration for the management of metastatic bone pain.

Topics: Adult; Aged; Analgesics; beta-Endorphin; Bone Neoplasms; Calcitonin; Dose-Response Relationship, Drug; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Prospective Studies

Plasma beta-endorphin levels were studied in the coronary sinus of 8 patients undergoing percutaneous transluminal coronary angioplasty (PTCA). All the patients had ECG ischemic signs and pain during the inflation of the balloon. No significant changes in plasma beta-endorphin levels were observed during PTCA-induced ischemia. Baseline coronary sinus plasma beta-endorphin levels were found to be elevated when compared with peripheral ones which would suggest an accumulation of beta-endorphin in the ischemic heart.

Topics: Aged; Angioplasty, Balloon, Coronary; beta-Endorphin; Coronary Disease; Coronary Vessels; Humans; Male; Pain; Reference Values

Peripheral afferent neuronal barrage from tissue injury produces central nervous system hyperexcitability which may contribute to increased postoperative pain. Blockade of afferent neuronal barrage has been reported to reduce pain following some, but not all, types of surgery. This study evaluated whether blockade of sensory input with a long-acting local anesthetic reduces postoperative pain after the anesthetic effects have dissipated. Forty-eight patients underwent oral surgery with general anesthesia in a parallel group, double-blind, placebo-controlled study. Subjects randomly received either 0.5% bupivacaine or saline intraoral injections, general anesthesia was induced with propofol, a non-opioid anesthetic, and 2-4 third molars extracted. Subjects were assessed at 24 and 48 h for postoperative pain and analgesic intake. Blood samples were collected at baseline, intraoperatively and at 1-h intervals postoperatively for measurement of beta-endorphin as an index of CNS response to nociceptor input. Plasma beta-endorphin levels increased significantly from baseline to the end of surgery in the saline group in comparison to the bupivacaine group (P < 0.05), indicating effective blockade of nociceptor input into the CNS by the local anesthetic. Pain intensity was not significantly different between groups at 24 h. Pain at 48 h was decreased in the bupivacaine group as measured by category scale and graphic rating scales for pain and unpleasantness (P < 0.05). Additionally, subjects in the bupivacaine group self-administered fewer codeine tablets for unrelieved pain over 24-48 h postoperatively (P < 0.05). These data support previous animal studies demonstrating that blockade of peripheral nociceptive barrage during and immediately after tissue injury results in decreased pain at later time points. The results suggest that blockade of nociceptive input by administration of a long-acting local anesthetic decreases the development of central hyperexcitability, resulting in less pain and analgesic intake.

Topics: Adult; Analgesics, Opioid; Anesthetics, Local; beta-Endorphin; Bupivacaine; Codeine; Double-Blind Method; Female; Humans; Male; Molar, Third; Nerve Block; Neurons, Afferent; Pain; Pain, Postoperative; Peripheral Nerves; Self Administration; Tooth, Impacted

The influence of anxiety on acute pain sensation was investigated, studying the relative contribution of endogenous opioids and attentional mechanisms. Thirty-six spider phobics received mildly painful electrical stimulation, while anxiety and focus of attention were manipulated within subjects. The opioid antagonist naloxone or placebo was administered between subjects to examine an analgesia owing to anxiety-induced endorphinergic activity. In contrast to earlier findings, attention towards pain failed to increase pain as opposed to distraction from pain, probably owing to a less effective attention manipulation. Furthermore, despite high levels of anxiety, subjective pain ratings were not influenced by anxiety, although heart rate responses were slightly inhibited. Accordingly, there was no increase in subjective or physiological pain responses as a result of naloxone, nor did beta-endorphin plasma levels rise during anxiety. The results suggest that phobic anxiety does not induce an opioid-mediated analgesia. Curiously, naloxone itself effected a dose-dependent analgesia compared to placebo during both high and low anxiety, which is compatible with the assumption of agonist properties of naloxone in the absence of opioid activity.

Topics: Adolescent; Adult; Analgesia; Analysis of Variance; Animals; Anxiety; Attention; beta-Endorphin; Cross-Over Studies; Female; Humans; Longitudinal Studies; Naloxone; Pain; Pain Measurement; Phobic Disorders; Spiders; Stress, Physiological

A quantitative analysis was performed of substance P-like immunoreactivity (SPLI) and of beta-endorphin-like immunoreactivity (beta-ENDLI), in the cerebrospinal fluid (CSF) in various diseases. The results reported to date have not been consistent. The purpose of this study was to investigate whether or not the concentration of SPLI or that of beta-ENDLI in CSF demonstrated any potential for assessing the degree of subjective pain in various spinal diseases. SPLI in CSF was measured by radioimmunoassay in 158 patients with a spinal disease; involving 57 patients with a lumbar disc herniation (LDH), 38 with lumbar canal stenosis (LCS), 46 with cervical myelopathy (CM) and 17 with cervical radiculopathy (CR), and also in 20 healthy controls. beta-ENDLI in CSF was measured in 25 of these same patients; involving 12 with LDH, seven with LCS and six with CM, and also five of the same controls. The concentration of serum SPLI was also measured in 50 of these 158. The severity of pain was self-evaluated by each patient using a linear visual analogue scale (VAS). Their Japanese Orthopaedic Association (JOA) score was also calculated objectively using the clinical findings. Correlations were investigated among the concentrations of SPLI and beta-ENDLI in the CSF and the VAS and JOA clinical assessments of these patients. The concentration of SPLI in CSF was significantly higher in various spinal diseases than in control (P < 0.05), and was correlated with the severity on the VAS and with the JOA score. However, beta-ENDLI was not correlated with either the VAS or the JOA score. We conclude that the measurement of the SPLI concentration in CSF has the potential for assessing objectively the severity of pain associated with various spinal diseases.

Topics: Activities of Daily Living; beta-Endorphin; Humans; Low Back Pain; Neuropeptides; Pain; Pain Measurement; Radioimmunoassay; Spinal Cord Diseases; Substance P

Whether i.v. infusion of beta-endorphin or metenkephalin can modify adenosine-provoked angina pectoris-like pain was investigated in healthy volunteers with a double-blind controlled design. All seven volunteers experienced dose-related adenosine-provoked chest pain. Metenkephalin did not modulate the dose-effect curve for adenosine while beta-endorphin counteracted (p < 0.01) the development of pain. The results suggest that peripheral p.subtype opioid receptors are involved in the modulation and may play a role in the genesis of silent and painful myocardial ischaemia.

Topics: Adult; Angina Pectoris; beta-Endorphin; Dose-Response Relationship, Drug; Double-Blind Method; Enkephalins; Humans; Male; Middle Aged; Pain

This study aimed at evaluating the effects of a dynamic physical training programme on circulating levels of corticotropin-releasing hormone (CRH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EP) after high-intensity training for 6 weeks (60 min twice a week) and after low-intensity training (home-training) for another 6 months in patients with rheumatoid arthritis (RA) and in healthy subjects. Additionally, differences in neuropeptide levels between the two groups were studied. A total of 30 patients with RA were randomly allocated to the study, 15 in the training group (TG) and 15 in the control group (CG). In addition, 20 healthy subjects (10 in TG; 10 in CG) participated. In addition to the biochemical analyses, the following variables were assessed for the RA group: pain and disability (Stanford health assessment questionnaire), joint tenderness (Ritchie articular index), disease activity, muscle function, aerobic capacity, sociodemographic data and attitudes. The results obtained at the start revealed significant differences (p < 0.05) between RA patients and healthy subjects concerning CRH levels, RA patients showing the lower levels (RA-group Md = 24 pmol/L, healthy group Md = 29 pmol/L). No significant differences concerning beta-LPH and beta-EP were found here. After the high-intensity training period, a significant increase of the CRH levels were found for the RA-TG (pretest Md = 24 pmol/L, after 6 weeks Md = 27 pmol/L, p < 0.05). No such results were found for the healthy-TG or the control groups. Concerning beta-EP, significant differences between the RA-TG and healthy-TG were found after the training. RA patients generally showing higher levels as compared with the healthy (RA-group Md = 42 pmol/L, healthy group Md = 36 pmol/L, p < 0.05). The same pattern was found for the beta-LPH levels. In conclusion, the effects of physical training on circulating neuropeptides remain still incompletely examined, and there is no definite answer to the question whether increased beta-EP levels are good or bad.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Female; Humans; Male; Middle Aged; Neuropeptides; Pain; Physical Education and Training

To determine whether the use of opioids could reduce the hypoxemia and hemodynamic instability associated with routine intensive care procedures in neonates with respiratory distress.. Randomized and placebo-controlled study.. Physiological, plasma beta-endorphin, cortisol, and glucose responses to routine treatment procedures were studied in 84 mechanically ventilated distressed neonates randomized into groups receiving 1 mg/kg meperidine or 0.9% saline 15 minutes before tracheal suction or routine nursing care.. The duration of hypoxemia (transcutaneous partial pressure of O2 < 6.6 kPa (< 50 mm Hg) and/or arterial blood oxygen saturation < 80%) during treatment procedures was significantly longer in the saline group (mean 82 vs 36 seconds, P = .001) and distress quantified by a novel behavioral scoring method was much higher. Changes in arterial blood pressure, heart rate, or plasma beta-endorphin, cortisol, and glucose concentration did not show any statistically significant differences between the groups.. Newborns with respiratory difficulties often suffer from hypoxemia during essential treatment procedures. The use of opioid analgesia may reduce the duration of hypoxemia and the associated distress and, therefore, may improve the long-term results of neonatal intensive care.

Topics: beta-Endorphin; Humans; Hydrocortisone; Hypoxia; Infant Care; Infant, Newborn; Meperidine; Oxygen; Pain; Respiratory Distress Syndrome, Newborn; Stress, Physiological; Suction

To investigate the role of the opioid system in the pathophysiology of silent ischemia through opiate antagonism with naloxone, and to determine the reproducibility of resting and postexercise beta-endorphin levels in predominantly asymptomatic patients with coronary artery disease.. Randomized, double-blind, placebo-controlled crossover trial.. A University hospital referral center.. Ten patients with prior evidence of silent exercise-induced ischemia were studied.. An infusion of saline placebo or naloxone at two dose regimens of 0.015 mg/kg or 0.15 mg/kg before supine exercise testing during three separate occasions for each patient.. Plasma beta-endorphin was measured at rest, immediately after exercise, and 5 min poststress. Timing and severity of angina and exercise hemodynamics were also determined.. Seven of 10 patients reported no angina, whereas the other three experienced angina with placebo and after administration of naloxone at both doses. The severity and duration of angina was consistently noted to decrease in these patients after naloxone administration, especially after low-dose naloxone relative to placebo. There were no apparent correlations between beta-endorphin levels and the characteristics of angina in these three patients, nor between beta-endorphin and hemodynamic responses in all patients in the study.. (a) naloxone failed to precipitate angina in this population of patients with silent ischemia; (b) naloxone appears to exert an analgesic effect at low doses; and (c) a variability of 5 pM at rest and 13 pM after exercise might be expected in predominantly asymptomatic patients due to random variation, which is comparable with results found in normal subjects.

Topics: Aged; Angina Pectoris; beta-Endorphin; Electrocardiography; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Naloxone; Pain; Receptors, Opioid; Reproducibility of Results

Although the analgesic effects observed during the application of vibration may be attributable to neuronal inhibition of the pain pathways, this does not account for the fact that pain relief sometimes persists for a long time after the end of vibration treatment. Two experiments were carried out in order to determine whether pain relief might involve the release of endogenous opioids. In the first experiment, we studied the effects of injecting either a morphine antagonist, naloxone (0.4 mg), or a placebo, on the analgesia resulting from vibratory stimulation in 12 patients suffering from acute or chronic pain. In the second experiment, the Met-enkephalin and beta-endorphin levels were determined before and after 30 min vibratory stimulation in the cerebrospinal fluid of 8 patients suffering from chronic pain and 1 control subject, all of whom had been fitted with a ventriculo-peritoneal drain which made it possible to collect samples of cerebrospinal fluid painlessly. The results of these experiments show, on the one hand, that the effects of naloxone on the vibration-induced analgesia did not differ from those of the placebo and, on the other hand, that no increase in the Met-enkephalin or beta-endorphin levels occurred concomitantly with pain relief. It will therefore be necessary to investigate other mechanisms as possible means of explaining the post-vibratory analgesic effects.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesia; beta-Endorphin; Female; Humans; Male; Middle Aged; Naloxone; Pain; Pain Measurement; Radioimmunoassay; Vibration

Hypnosis and acupuncture can alleviate experimentally induced pain but the mechanism of analgesia remains unclear for both techniques. Experimental pain was induced by cold pressor test (CPT) in 8 male volunteers. Analgesic effect of hypnosis (HA) and acupuncture (AA) was assessed before and after double-blind administration of placebo or naloxone, in a prospective, cross-over study. We found that pain intensity was significantly lower with HA as compared with AA, both with naloxone (P less than 0.001) and placebo (P less than 0.001). Within HA or AA groups, pain scores did not differ significantly when naloxone or placebo was administered. During AA, however, pain scores were similar to control values when naloxone was given (P = 0.05) but decreased significantly with placebo (P less than 0.002). Analog scales for pain intensity and pain relief showed a good correlation (r = 0.94). Plasma levels of beta-endorphins did not change significantly in any combination. Heart rate, peripheral arterial blood pressure and skin conductance were very insensitive indices to assess pain intensity or relief, as well as intensity of acupuncture stimulation or depth of hypnotic trance. We conclude: (1) HA and AA can significantly reduce pain from CPT, and HA is more effective than AA: (2) HA and AA are not primarily mediated by the opiate endorphin system; and (3) plasmatic levels of beta-endorphins are not significantly affected by either HA or AA nor by naloxone or placebo administration.

Topics: Acupuncture Analgesia; Adult; Affect; Analgesia; beta-Endorphin; Blood Pressure; Heart Rate; Humans; Hypnosis; Male; Naloxone; Pain; Pain Management; Pain Measurement; Reference Values; Skin Physiological Phenomena

Experimental pain thresholds (electrical intracutaneous finger and dental pulp stimulation) and plasma hormone levels (beta-endorphin, cortisol, and catecholamines) were measured in ten healthy sportive men before, during, and after progressively more strenuous physical exercise. In a double-blind study conducted on two different days, 20 mg of the opioid-antagonist naloxone or placebo was administered prior to exercise. A significant pain threshold elevation was found during exercise for finger (ANOVA, P less than 0.004) and dental pulp stimulation (P less than 0.01). Pain threshold elevation was most pronounced during maximal exertion, at which time the subjects reported the greatest subjective fatigue. Thresholds remained elevated 10-15 min after the end of exercise, and, 60 min after exercise, thresholds returned to baseline values. The subjective magnitude estimation of suprathreshold stimuli was significantly reduced (P less than 0.0001) 5-10 min after exercise. Plasma beta-endorphin, cortisol, and catecholamines increased significantly (P less than 0.0005, all values) during exercise. Plasma beta-endorphin levels did not correlate significantly with pain thresholds (r = -0.37, NS). Naloxone failed to affect pain thresholds, although beta-endorphin and cortisol increased significantly more (P less than 0.02) during exercise after naloxone. It is concluded that short-term, exhaustive physical exercise can evoke a transient elevation in pain thresholds. This exercise-induced elevation in pain threshold does not, however, appear to be directly related to plasma endorphin levels.

Topics: Adult; Analysis of Variance; beta-Endorphin; Bicycling; Double-Blind Method; Epinephrine; Exercise; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Norepinephrine; Pain; Sensory Thresholds

During a 5 month, double blind crossover study of the clinical effect of cyclobenzaprine on 7 patients with fibrositis, weekly measurements were done of plasma beta-endorphin (endorphin, prostaglandin E (PGE) and catecholamines). Endorphin levels were normal but varied with tender point tenderness. Mean plasma dopamine and PGE were elevated. Norepinephrine was normal to very high while epinephrine levels were continuously low to normal. We conclude that patients with fibrositis have a neurotransmitter plasma profile like other chronic pain states having stress and increased vasomotor activity with the possible exception of having low circulating epinephrine. This disparity may mark a failure of central nervous system pain modulation in fibrositis.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; beta-Endorphin; Catecholamines; Dinoprostone; Double-Blind Method; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain; Placebos; Sleep

The effect of acupuncture on sensory thresholds was studied in 6 healthy subjects. The modes of acupuncture studied were: 1. manual stimulation, 2. electrical stimulation at 2 Hz, 3. electrical stimulation at 80 Hz. Superfiscial-acupuncture was used as placebo. Insertions of needles or application of electrodes were bilateral, at St 7 (intrasegmental) or Li 4 (extrasegmental). The study showed that manual or electro-acupuncture were effective when used intrasegmentally, raising pain threshold values 1.1 to 1.4 times that prior to stimulation. The pain threshold elevation obtained was not significantly related to plasma levels of beta-endorphin, ACTH or prolactin. Other sensory thresholds, thermal, vibrotactile and electrotactile were unaffected by such conditioned stimulation. Superfiscial-acupuncture had no significant effect on the sensory thresholds tested.

Topics: Acupuncture Analgesia; Acupuncture Therapy; Adolescent; Adult; beta-Endorphin; Blood Pressure; Electroacupuncture; Evaluation Studies as Topic; Female; Heart Rate; Humans; Male; Naloxone; Pain; Pain Measurement; Sensory Thresholds; Thermosensing; Touch

The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of beta-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were assessed in 17 trained, male runners before and after running the longest possible distance within 12 min (i.e., the Cooper test). Each runner participated twice in the test (double-blind cross-over design), with a 1-week interval--with or without an injection of the opiate antagonist naloxone (0.8 mg i.v.). The average (SEM) distance reached was 3,198 (45) m in the naloxone test and 3,240 (38) m in the placebo test. The BEP increased significantly during the tests by a factor of 4.1 on naloxone and by 2.8 on placebo (from the normal resting averages of 1.7 and 2.1 pmol/l, respectively). The ACTH also increased significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of 19.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle pain was enhanced with naloxone. The increased perception of pain did not decrease the athletes ability to perform in terms of the distance run. We conclude that endogenous opiates are involved in the perception of pain associated with exhaustive exercise and may subserve psychological rather than physiological functions during exercise.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Exercise; Humans; Male; Pain; Perception; Physical Endurance

The neuroendocrine effects of 5 and 10 mg of oral diazepam were assessed in 10 normal subjects under baseline (prestress) and laboratory-controlled stressful conditions. Although the 10-mg diazepam dose had no effect on cortisol at baseline, it significantly reduced the increase in cortisol produced by 15 minutes of exposure to a painful electrical stimulus. There were no significant effects on growth hormone, beta-endorphin or ACTH, either at baseline or after painful stimulation.

Topics: Adult; beta-Endorphin; Diazepam; Humans; Hydrocortisone; Male; Pain; Stress, Physiological

We conducted this study to evaluate the effect of massage on the levels of endogenous opiates in peripheral venous blood. The results were based on findings from 21 healthy, adult volunteers. After separation by sex, the volunteers were assigned randomly to either the Control Group (n = 11) that rested but received no massage or the Experimental Group (n = 10) that received a 30-minute complete back massage. We found no significant pretreatment or posttreatment difference in blood beta-endorphin or beta-lipotropin levels between the groups. The results indicate that massage did not change significantly the measured serum levels of beta-endorphin or beta-lipotropin in our healthy subjects without pain. A follow-up study using patients experiencing acute or chronic back pain is recommended. Massage is used routinely in the treatment of such patients, and endogenous opiates are recognized as a possible mechanism for pain relief.

Topics: Adult; beta-Endorphin; beta-Lipotropin; Endorphins; Female; Humans; Male; Massage; Pain; Pain Management

This study was designed to examine the effects of aspirin, naloxone and placebo treatment on serum beta-endorphin concentration and joint pain in patients with rheumatoid arthritis (RA). Ten patients with definite or classical RA were studied. All treatments were administered in a randomized sequence. On each study day, the following measurements were carried out at specified time intervals: serum beta-endorphin concentration, serum salicylate concentration and joint pain score on a visual analogue horizontal scale. We conclude that in patients with rheumatoid arthritis suffering from chronic joint pain, serum beta-endorphin does not appear to play a role in pain relief.

Topics: Arthritis, Rheumatoid; Aspirin; beta-Endorphin; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Humans; Naloxone; Pain; Pain Measurement; Placebos; Random Allocation

Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week, randomized, double-blind comparison of doxepin and placebo. Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores, Global Assessment Scale scores, pain severity, percent of time pain felt, and effect of pain on activity, sleep, and muscle tension. Some improvements were observed after 1 week of treatment; the most improvement occurred at 6 weeks, when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml. No significant harmful effects were observed. Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline. These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression.

Topics: beta-Endorphin; Chronic Disease; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Doxepin; Endorphins; Enkephalins; Female; Humans; Male; Middle Aged; Pain; Placebos; Psychiatric Status Rating Scales; Random Allocation; Time Factors

The effects of intense exercise on pain perception, mood, and plasma endocrine levels in man were studied under naloxone and saline conditions. Twelve long-distance runners (mean weekly mileage = 41.5) were evaluated on thermal, ischemic, and cold pressor pain tests and on mood visual analogue scales (VAS). Blood was drawn for determination of plasma levels of beta-endorphin-like immunoreactivity (BEir), growth hormone (GH), adrenocorticotrophic hormone (ACTH), and prolactin (PRL). These procedures were undertaken before and after a 6.3 mile run at 85% of maximal aerobic capacity. Subjects participated on two occasions in a double-blind procedure counterbalanced for drug order: on one day they received 2 i.v. injections of naloxone (0.8 mg in 2 ml vehicle each) at 20 min intervals following the run; on the other day, 2 equal volume injections of normal saline (2 ml). Sensory decision theory analysis of the responses to thermal stimulation showed that discriminability, P(A), was significantly reduced post-run under the saline condition, a hypoalgesic effect; response bias, B, was unaffected. Ischemic pain reports were significantly reduced post-run on the saline day, also a hypoalgesic effect. Naloxone reversed the post-run ischemic but not thermal hypoalgesic effects. Joy, euphoria, cooperation, and conscientiousness VAS ratings were elevated post-run; naloxone attenuated the elevation of joy and euphoria ratings only. Plasma levels of BEir, ACTH, GH, and PRL were significantly increased post-run. The results show that long-distance running produces hypoalgesia and mood elevation in man. The effects of naloxone implicate endogenous opioid neural systems as mechanisms of some but not all of the run-induced alterations in mood and pain perception.

Topics: Adrenocorticotropic Hormone; Adult; Affect; beta-Endorphin; Endorphins; Growth Hormone; Hormones; Humans; Male; Naloxone; Pain; Physical Exertion; Prolactin; Running; Sensory Thresholds

Thirty patients with chronic low back or cervical pain combined with clinical depression were studied in a six-week, randomized, double-blind comparison of doxepin and placebo. Dependent variables included Hamilton Depression Scores, the Clinical Global Assessment Scale, and Profile of Mood States (POMS), and subjective ratings (visual analogue scales) of pain severity, percent of time pain felt, and effect of pain on activity, muscle tension, sleep, mood, and analgesic drug consumption. Plasma levels of doxepin, desmethyldoxepin, beta-endorphin, and enkephalin-like activity were also measured. Significant improvements in the doxepin-treated group compared to the placebo group were seen in Hamilton scores, Global Assessment Scale, Profile of Mood States, percent of time pain felt, and effect of pain on sleep, muscle tension, and mood. Some improvement was observed after 1 week, although most improvement occurred at 6 weeks, when the mean doxepin dose was 2.5 mg/kg and plasma doxepin and desmethyldoxepin averaged 70 ng/ml. Nonspecific enkephalin-like activity (but not beta-endorphins) increased for the treatment group and decreased for the placebo group. The efficacy of doxepin compared with that of placebo was thus documented in several depressive and pain parameters, indicating that doxepin is a valuable treatment for patients with chronic pain and depression.

Topics: Adult; Aged; beta-Endorphin; Chronic Disease; Depression; Double-Blind Method; Doxepin; Endorphins; Enkephalins; Female; Humans; Male; Middle Aged; Pain; Placebos; Random Allocation; Sensory Thresholds; Sleep

The effect of ceruletide (CRL), a synthetic decapeptide analogue of cholecystokinin, on rest pain and arterial blood flow was evaluated in 8 patients with advanced, occlusive atherosclerosis of the lower extremities. CRL 1, 2, or 4 ng kg-1 or placebo were infused intravenously in random order, and in a double-blind fashion. Pain relief, assessed by a scoring system, was significantly better (p less than 0.01) following the 2 and 4 ng kg-1 doses of CRL (2.71 and 2.66, respectively) than following placebo (0.75). Arterial blood flow was not affected by either CRL in any dose or by placebo. Pretreatment with naloxone, a pure opioid antagonist, abolished the analgesic effect of CRL. Following the 2 ng dose of CRL, beta-endorphin levels were significantly elevated from a basal value of 125 +/- 15 pg/ml to 191 +/- 35 pg/ml 5 h after CRL administration (p less than 0.05). Circulating levels of ACTH, prolactin and GH were not affected by CRL. It is concluded that CRL was effective in relieving ischaemic rest pain, and that the mechanism was related to the release of endogenous opioids.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arteriosclerosis; beta-Endorphin; Ceruletide; Endorphins; Female; Gas Gangrene; Humans; Leg; Leg Ulcer; Male; Middle Aged; Naloxone; Pain; Rest

Tiapride, a substituted benzamide, exerts an antalgic effect in man. To examine the possibility that tiapride analgesia might be related to a mechanism involving a release of endogenous opioids, the acute effects of an intravenous injection of the drug on plasma radioimmunoassayable beta-endorphin were studied in patients with pain from cancer (placebo-tiapride double-blind randomized trial). Seeing that substituted benzamides affect prolactin secretion, the plasmatic levels of prolactin and dopamine, a known factor inhibiting prolactin release, were studied as well. The tiapride infusion produced a slight but significant increase in plasma beta-endorphin level, an early and significant increase in plasma prolactin, and a sudden and highly significant decrease in plasma dopamine. These results are compatible with the hypothesis that tiapride influences the neuroendocrine system.

Topics: Adrenocorticotropic Hormone; Aged; Benzamides; beta-Endorphin; Dopamine; Endorphins; Female; Humans; Male; Neoplasms; Pain; Prolactin; Tiapamil Hydrochloride

The nucleus of the solitary tract (NTS) contains pro-opiomelanocortin (POMC) neurons that are 1 of the 2 major sources of β-endorphin in the brain. The functional role of these NTS POMC neurons in nociceptive and cardiorespiratory function is debated. We have shown that NTS POMC optogenetic activation produces bradycardia and transient apnoea in a working heart-brainstem preparation and chemogenetic activation with an engineered ion channel (PSAM) produced opioidergic analgesia in vivo. To better define the role of the NTS POMC neurons in behaving animals, we adopted in vivo optogenetics (ChrimsonR) and excitatory/inhibitory chemogenetic DREADD (hM3Dq/hM4Di) strategies in POMC-Cre mice. We show that optogenetic activation of NTS POMC neurons produces time-locked, graded, transient bradycardia and bradypnoea in anaesthetised mice that is naloxone sensitive (1 mg/kg, i.p.), suggesting a role of β-endorphin. Both optogenetic and chemogenetic activation of NTS POMC neurons produces sustained thermal analgesia in behaving mice that can be blocked by naloxone. It also produced analgesia in an inflammatory pain model (carrageenan) but not in a neuropathic pain model (tibial nerve transection). Inhibiting NTS POMC neurons does not produce any effect on basal nociception but inhibits stress-induced analgesia (unlike inhibition of arcuate POMC neurons). Activation of NTS POMC neuronal populations in conscious mice did not cause respiratory depression, anxiety, or locomotor deficit (in open field) or affective preference. These findings indicate that NTS POMC neurons play a key role in the generation of endorphinergic endogenous analgesia and can also regulate cardiorespiratory function.

Topics: Analgesia; Animals; beta-Endorphin; Bradycardia; Mice; Naloxone; Neurons; Pain; Pro-Opiomelanocortin; Solitary Nucleus

The efficacy of acupuncture in treating pain diseases has been recognized in clinical practice, and its mechanism of action has been a hot topic in academic acupuncture research. Previous basic research on acupuncture analgesia has focused mostly on the nervous system, with few studies addressing the immune system as a potential pathway of acupuncture analgesia. In this study, we investigated the effect of electroacupuncture (EA) on the β-endorphins (β-END) content, END-containing leukocyte type and number, sympathetic neurotransmitter norepinephrine (NE), and chemokine gene expression in inflamed tissues. To induce inflammatory pain, about 200 µL of complete Frester adjuvant (CFA) was injected into the unilateral medial femoral muscle of adult Wistar rats. Electroacupuncture treatment was performed for 3 days beginning on day 4 after CFA injection, with parameters of 2/100 Hz, 2 mA, and 30 minutes per treatment. The weight-bearing experiment and enzyme-linked immunosorbent assay showed that EA treatment significantly relieved spontaneous pain-like behaviors and increased the level of β-END in inflamed tissue. Injection of anti-END antibody in inflamed tissue blocked this analgesic effect. Flow cytometry and immunofluorescence staining revealed that the EA-induced increase in β-END was derived from opioid-containing ICAM-1 + /CD11b + immune cells in inflamed tissue. In addition, EA treatment increased the NE content and expression of β2 adrenergic receptor (ADR-β2) in inflammatory tissues and upregulated Cxcl1 and Cxcl6 gene expression levels. These findings provide new evidence for the peripheral analgesic effect of acupuncture treatment by recruiting β-END-containing ICAM-1 + /CD11b + immune cells and increasing the β-END content at the site of inflammation.

Topics: Acupuncture Analgesia; Analgesics; Animals; beta-Endorphin; Electroacupuncture; Intercellular Adhesion Molecule-1; Neutrophils; Pain; Rats; Rats, Wistar

Chronic widespread pain (CWP) is associated with a high rate of disability and decreased quality of life in people with HIV-1 (PWH). We previously showed that PWH with CWP have increased hemolysis and elevated plasma levels of cell-free heme, which correlate with low endogenous opioid levels in leukocytes. Further, we demonstrated that cell-free heme impairs β-endorphin synthesis/release from leukocytes. However, the cellular mechanisms by which heme dampens β-endorphin production are inconclusive. The current hypothesis is that heme-dependent TLR4 activation and macrophage polarization to the M1 phenotype mediate this phenomenon. Our novel findings showed that PWH with CWP have elevated M1-specific macrophage chemokines (ENA-78, GRO-α, and IP-10) in plasma. In vitro, hemin-induced polarization of M0 and M2 macrophages to the M1 phenotype with low β-endorphins was mitigated by treating cells with the TLR4 inhibitor, TAK-242. Similarly, in vivo phenylhydrazine hydrochloride (PHZ), an inducer of hemolysis, injected into C57Bl/6 mice increased the M1/M2 cell ratio and reduced β-endorphin levels. However, treating these animals with the heme-scavenging protein hemopexin (Hx) or TAK-242 reduced the M1/M2 ratio and increased β-endorphins. Furthermore, Hx attenuated heme-induced mechanical, heat, and cold hypersensitivity, while TAK-242 abrogated hypersensitivity to mechanical and heat stimuli. Overall, these results suggest that heme-mediated TLR4 activation and M1 polarization of macrophages correlate with impaired endogenous opioid homeostasis and hypersensitivity in people with HIV.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Heme; Hemolysis; HIV Infections; Homeostasis; Macrophages; Mice; Pain; Phenotype; Quality of Life; Toll-Like Receptor 4

The opioid peptide β-endorphin coexists in the pituitary and brain in its

Topics: Animals; beta-Endorphin; GTP-Binding Proteins; Ligands; Mice; Morphine; Pain; Receptors, Opioid; Receptors, Opioid, mu; Receptors, sigma

We investigated acupuncture, a potential contributor for burn care, on physiological and pathological pain mechanisms and systemic and local inflammatory responses in a rat experimental burn model. Forty male Sprague-Dawley rats were divided into two groups. One-hour groups (five rats/group) were observed for 1 hour and included Sh1 (sham/observation), ShA1 (sham + acupuncture/observation), Brn1 (burn/observation), and BrnA1 (burn + acupuncture/observation). Seven-day groups (five rats/group) were observed for 7 days and included Sh7 (sham/observation), ShA7 (sham + acupuncture/observation), Brn7 (burn/observation), and BrnA7 (burn + acupuncture/observation). "Pain-distress scores" were noted daily, and acupuncture was repeated within every wound-dressing change on alternate days. After observation periods, blood samples for interleukin 6 and beta-endorphin and skin biopsies for inflammatory changes and immunohistochemical staining of interleukin 6 were collected for analysis(P < .05). In 1-hour groups, interleukin 6 accumulation in burn wounds of BrnA1 was less than Brn1, with Brn1 having the highest mean blood level (P < .05). Mean beta-endorphin levels were higher in ShA1, Brn1, and BrnA1 than in Sh1 (P < .05). In all 7-day groups, the agonizing period was 48 to 72 hours after burn, with Brn7 most affected (P < .05). Microvessels were multiplied in the Brn7 group, with significantly higher numbers in burn wounds of BrnA7 (P ˂ .05). Burn wounds of BrnA7 had less accumulation of interleukin 6 than Brn7 with the Brn7 group having the highest mean blood level and Sh7, ShA7, and BrnA7 having similarly low levels (P ˃ .05). Beta-endorphin levels in ShA7, Brn7, and BrnA7 were lower than in Sh7 (P < .05). Acupuncture contributed to the management of physiological and pathological pain, modulation of inflammatory responses, and associated enhancement of angiogenesis in the acute phase of burn injury in rats.

Topics: Acupuncture Therapy; Animals; beta-Endorphin; Burns; Interleukin-6; Male; Pain; Rats; Rats, Sprague-Dawley; Wound Healing

Beta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential relationship in adolescents with NSSI.. 94 adolescents with NSSI (according to DSM-5 criteria) and 35 healthy controls (HC) were enrolled. All participants received heat pain stimulation, with pain threshold and tolerance measured in °C. Plasma BE levels were assessed. Sociodemographic and clinical characteristics were obtained via semi-structured interviews and self-report questionnaires.. Future studies should implement repeated plasma BE measures to assess BE release in association with pain in NSSI. Validity of plasma BE measures compared to central measures should be considered. Assessing the association between pain sensitivity (PS) and BE in a naturalistic setting presents a promising avenue for future research in NSSI.. Findings support both reduced PS and basal opioid deficiency as independent biological correlates and potential risk-factors for NSSI. Further longitudinal and experimental studies are needed to investigate the role of BE levels and PS as well as their potential association.

Topics: Adolescent; beta-Endorphin; Borderline Personality Disorder; Humans; Pain; Pain Threshold; Plasma; Self-Injurious Behavior

Nonsuicidal self-injury (NSSI) is a prevalent and impairing behavior, affecting individuals with and without additional psychopathology. To shed further light on biological processes that precede and result from NSSI acts, we built on previous cross-sectional evidence suggesting that the endogenous opioid system, and especially β-endorphin, is involved in the psychopathology of NSSI. This is the first study assessing salivary β-endorphin in daily life in the context of NSSI acts. Fifty-one female adults with repetitive NSSI participated over a period of 15 days in an ambulatory assessment study. Salivary β-endorphin was assessed before and after engagement in NSSI, during high urge for NSSI, and on a non-NSSI day. Furthermore, NSSI specific variables such as pain ratings, as well as method, severity, and function of NSSI were assessed. We found that β-endorphin levels immediately before an NSSI act were significantly lower than directly after NSSI. However, there was no difference between β-endorphin during high urge for NSSI and post NSSI measures. We found a positive association between severity of the self-inflicted injury and β-endorphin levels, but no significant association between β-endorphin levels and subjectively experienced pain. The results of the present study indicate that it is possible to assess salivary β-endorphin in daily life in the context of NSSI. Furthermore, our results provide a first indication that NSSI acts could be associated with a momentary increase of β-endorphin, and this might reinforce NSSI engagement. More research is needed to replicate and extend our findings on peripheral β-endorphin in daily life.

Topics: Adult; beta-Endorphin; Cross-Sectional Studies; Female; Humans; Pain; Self-Injurious Behavior

Pain caused by soft tissue injury (STI) is always intractable and will eventually result in physical and psychological problems. This experiment aimed to assess the efficacy and mechanisms of low-intensity focused ultrasound (LIFU) for pain-related STI.. Rabbits (n = 30) with STI were given fixed treatment for 20 seconds and then mobile treatment for 60 seconds daily for 10 consecutive days by an LIFU device with a power output of 5 to 6 W and a frequency of 0.8 MHz. To evaluate the degree of pain, the levels of β-endorphin in serum were measured by an enzyme-linked immunosorbent assay before and 5 to 10 minutes after the 1st, 3rd, 7th, and 10th treatments. The pain threshold was measured by an electronic analgesy meter on the 1st, 3rd, 7th, 10th, 17th, and 24th days after the start of the treatment. To investigate inflammation, prostaglandin E. Compared with non-LIFU groups, β-endorphin levels and pain thresholds were significantly increased (P < .05), whereas nuclear factor- κB messenger RNA, prostaglandin E. Low-intensity focused ultrasound can alleviate pain induced by STI and could have further clinical applications.

Topics: Animals; beta-Endorphin; Disease Models, Animal; Pain; Pain Management; Pain Measurement; Rabbits; Soft Tissue Injuries; Treatment Outcome; Ultrasonic Therapy

The prevalence of chronic widespread pain (CWP) in people with HIV is high, yet the underlying mechanisms are elusive. Leukocytes synthesize the endogenous opioid, β-endorphin, within their endoplasmic reticulum (ER). When released into plasma, β-endorphin dampens nociception by binding to opioid receptors on sensory neurons. We hypothesized that the heme-dependent redox signaling induces ER stress, which attenuates leukocyte β-endorphins levels/release, thereby increasing pain sensitivity in people with HIV. Results demonstrated that HIV positive individuals with CWP had increased plasma methemoglobin, erythrocytes membrane oxidation, hemolysis, and low plasma heme scavenging enzyme, hemopexin, compared to people with HIV without CWP and HIV-negative individuals with or without pain. In addition, the leukocytes from people with HIV with CWP had attenuated levels of the heme metabolizing enzyme, heme oxygenase-1, which metabolizes free heme to carbon-monoxide and biliverdin. These individuals also had elevated ER stress, and low β-endorphin in leukocytes. In vitro, heme exposure or heme oxygenase-1 deletion, decreased β-endorphins in murine monocytes/macrophages. Treating cells with a carbon-monoxide donor or an ER stress inhibitor, increased β-endorphins. To mimic hemolytic effects in a preclinical model, C57BL/6 mice were injected with phenylhydrazine hydrochloride (PHZ). PHZ increased cell-free heme and ER stress, decreased leukocyte β-endorphin levels and hindpaw mechanical sensitivity thresholds. Treatment of PHZ-injected mice with hemopexin blocked these effects, suggesting that heme-induced ER stress and a subsequent decrease in leukocyte β-endorphin is responsible for hypersensitivity in people with HIV.

Topics: Animals; beta-Endorphin; Heme; HIV Infections; Leukocytes; Mice; Mice, Inbred C57BL; Pain

Analgesia with opioids such as morphine is an effective clinical strategy for the treatment of cancer pain and chronic inflammatory pain. However, long-term use of morphine can cause morphine tolerance (MT), which limits the clinical application of opioids. Polysaccharopeptide from Trametes versicolor (TPSP) is a biologically active macromolecule that exerts anti-tumor, immune-enhancing and pain-relieving effects. In order to address the clinical problem of MT, herein, we investigated the inhibitory effect and mechanism of TPSP in rats with inflammatory pain-morphine tolerance. A chronic inflammatory osteoarthritis pain-morphine tolerance model was simulated by injection of complete Freund's adjuvant (CFA) through the ankle joint cavity and continuous intrathecal administration of morphine. Different doses of TPSP (50 μg/kg, 100 μg/kg and 200 μg/kg) were intrathecally administered for consecutive 3 weeks. Our results indicate that TPSP can significantly inhibit the development of morphine dependence and acute withdrawal in rats, alleviate the decrease of paw withdrawal mechanical threshold and heat stimulation retraction latency. In addition, mechanistically at the molecular level, these effects are elicited via up-regulation of the cannabinoid type 2 receptor, up-regulating the level of β-endorphin, and reducing the levels of IL-1, NO and PGE

Topics: Animals; Behavior, Animal; beta-Endorphin; Dinoprostone; Down-Regulation; Inflammation; Interleukin-1; Male; Morphine; Nitric Oxide; Osteoarthritis; Pain; PC12 Cells; Proteoglycans; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Recombinant Proteins; Trametes

Ghrelin is an endogenous ligand for orphan growth hormone secretagogue receptors. Ghrelin receptors have been found in central nervous system (CNS) areas responsible for pain modulation and transmission. This study investigated the effects of intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin on pain behavioral responses and levels of β-endorphin (β-EP) and met-enkephalin (MENK) in the periaqueductal gray area (PAG) during the formalin test in rats. Thirty-five male rats were studied in five groups. Ghrelin was injected into the left lateral ventricle (ICV, 5 µL) or into the ARC (1 µL). After 15 min, formalin (2.5%) was subcutaneously injected into the left hind paw. Behavioral nociceptive scores were recorded for 60 min. MENK and β-EP were collected by microdialysis in the PAG and determined by high-performance liquid chromatography (HPLC). ICV and ARC injection of ghrelin significantly reduced pain in all phases of the formalin test (

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Enkephalin, Methionine; Ghrelin; Injections; Male; Pain; Pain Measurement; Periaqueductal Gray; Rats

The present study examined the co-expression of neuronal nitric oxide synthase (nNOS) in the rostral ventromedial medulla (RVM) and A5 regions of the mouse brainstem within several neurochemical populations involved in nociceptive modulation. Double immunohistochemical methods showed that nNOS+ neurons do not co-localize with serotonergic neurons within any of these regions. Within the RVM, the nuclei raphe magnus and gigantocellularis contain a population of nNOS+/GAD67+ neurons, and within the paragigantocellularis lateralis, there is a smaller population of nNOS+/CHAT+ neurons. Further, nNOS+ neurons overlap the region of expression of β-endorphinergic and met-enkephalinergic fibers within the RVM. No co-labeling was found within the A5 for any of these populations. These findings suggest that pain-modulatory serotonergic neurons within the brainstem do not directly produce nitric oxide (NO). Rather, NO-producing neurons within the RVM belong to GABAergic and cholinergic cell populations, and are in a position to modulate or be modulated by local opioidergic neurons.

Topics: Animals; beta-Endorphin; Brain Stem; Cholinergic Neurons; Enkephalins; GABAergic Neurons; Male; Medulla Oblongata; Mice; Midbrain Raphe Nuclei; Nitric Oxide Synthase Type I; Pain; Prefrontal Cortex; Receptors, Opioid; Serotonergic Neurons; Serotonin

This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), in magnitude as well as time course. Eight younger and 9 older adults underwent 3 experimental sessions using well validated laboratory pain models: cold pressor task, contact heat pain, and a nonpainful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60 minutes after stimuli administration. Older adults had higher baseline levels of both neuropeptides suggesting increased peripheral activity compared with younger adults. After the cold pressor task, older adults demonstrated a quick and strong release of substance P with dramatic recovery, whereas young adults maintained a constant low-grade response. Unlike substance P, β-endorphin increased between 3 and 15 minutes for both groups with the upsurge substantially higher for older adults. After heat pain, younger adults had an immediate surge in circulating substance P and β-endorphin that was more pronounced than among older adults. However, levels of substance P for younger adults slowly tapered whereas they continued to climb for the older adults through 30 minutes. β-endorphin peaked at 30 minutes for both groups and returned to baseline. No changes were observed during the nonpainful control session.. Older adults had higher baseline levels of substance P and β-endorphin suggesting increased peripheral activity compared with younger adults. After pain evocation, older adults demonstrated a more intense early response for both neuropeptides suggesting peripheral mechanisms involved in the response to pain may change with age.

Topics: Aged; Aging; Analysis of Variance; beta-Endorphin; Biomarkers; Cold Temperature; Female; Hot Temperature; Humans; Male; Pain; Pressure; Substance P; Time Factors; Young Adult

Pain in neonates is associated with short and long-term adverse outcomes. Data demonstrated that long-term consequences of untreated pain are linked to the plasticity of the neonate's brain. Sucrose is effective and safe for reducing painful procedures from single events. However, the mechanism of sucrose-induced analgesia is not fully understood. The role of the opioid system in this analgesia using the opioid receptor antagonist Naltrexone was investigated, plus the long-term effects on learning and memory formation during adulthood. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution and/or naltrexone were administered before the pricks. All treatments started on day one of birth and continued for two weeks. At the end of 8weeks, behavioral studies were conducted to test spatial learning and memory using radial arm water maze (RAWM), and pain threshold via foot-withdrawal response to a hot plate. The hippocampus was dissected; levels of brain derived neurotrophic factor (BDNF) and endorphins were assessed using ELISA. Acute repetitive neonatal pain increased pain sensitivity later in life, while naltrexone with sucrose decreased pain sensitivity. Naltrexone and/or sucrose prevented neonatal pain induced impairment of long-term memory, while neonatal pain decreased levels of BDNF in the hippocampus; this decrease was averted by sucrose and naltrexone. Sucrose with naltrexone significantly increased β-endorphin levels in noxiously stimulated rats. In conclusion, naltrexone and sucrose can reverse increased pain sensitivity and impaired long-term memory induced by acute repetitive neonatal pain probably by normalizing BDNF expression and increasing β-endorphin levels.

Topics: Animals; Animals, Newborn; beta-Endorphin; Brain-Derived Neurotrophic Factor; Dietary Sucrose; Hippocampus; Male; Maze Learning; Memory, Long-Term; Naltrexone; Narcotic Antagonists; Pain; Pain Management; Pain Threshold; Random Allocation; Rats, Wistar; Spatial Memory

Immune cell-derived beta-endorphin (END) and other opioid peptides elicit potent and clinically relevant inhibition of pain (analgesia) in inflamed tissue by activation of peripheral opioid receptors. Pro-opiomelanocortin (POMC) is the polypeptide precursor of END and is processed by prohormone convertases (PCs). This study aims to decipher the processing of POMC in lymphocyte subsets in a rat model of unilateral painful hindpaw inflammation. Lymphocytes, isolated from popliteal lymph nodes, were separated into B-cells, T-cells, T-helper cells and cytotoxic T-cells using magnetic cell sorting, and were examined by polymerase chain reaction, immunofluorescence and radioimmunoassay. At 2 h of inflammation, POMC exon 2-3 mRNA was mostly expressed in B- but not in T-cells. Prohormone convertase 1 (PC1) mRNA and protein were upregulated in B-cells and T-helper cells. Prohormone convertase 2 (PC2) was expressed in T- and B-cells, both in inflamed and non-inflamed lymph nodes. END was expressed in B- but not in T-cells. We conclude that POMC, its processing enzymes and END are predominantly expressed in B-lymphocytes at 2 h of paw inflammation.

Topics: Animals; B-Lymphocytes; beta-Endorphin; Gene Expression; Inflammation; Male; Pain; Pro-Opiomelanocortin; Proprotein Convertase 1; Proprotein Convertase 2; Rats; Rats, Wistar; RNA, Messenger; Serine Endopeptidases

To investigate the mechanism of cinobufagin-reduced cancer pain in mouse cancer pain model and in vitro cell co-culture system.. Female Kunming mice were randomly divided into 4 groups. One group of animals was set as normal control without any treatment. Other three groups of animals received H22 hepatoma cell inoculation in right hind paw. At day 9 after inoculation, mice in other three groups were injected intraperitoneally once a day for 8 days with the solvent, morphine or cinobufagin, respectively. The pain behavior was recorded daily. On the last day, all mice were sacrificed and xenograft tissues homogenate and plasma levels of β-endorphin (β-END), corticotropin-releasing factor (CRF) and interleukin-1β (IL-1β) were assessed by ELISA assay. Immunohistochemistry was performed to determine the expression of β-END, pro-opiomelanocortin (POMC) and the μ-opioid receptor (μ-OR) in the xenograft tissues. Immunofluorescence was used to localize lymphocytes with expression of CD3+, CD4+ and CD8+ in xenograft tumors and adjacent tissues. Mice splenic lymphocytes and H22 hepatoma carcinoma ascites cells were prepared for co-culture. β-END and CRF were detected in co-culture supernatants. The MTT assay and cytometry were used to assess cell proliferation. RT-PCR was conducted to determine the gene expression of POMC and Cathepsin L (CTSL). Chemotaxis was examined using a transwell-based migration assay.. Compared to the model group, the thermal and mechanical pain thresholds were increased in mice after cinobufagin treatment. The expression of β-END and CRF in the plasma and tumor tissues of cinobufagin group were much higher than that of the model group mice, but the expression of IL-1β in the plasma and tumor tissues was much lower than that in the model group mice. Meanwhile, the expression of β-END, POMC and μ-OR proteins was significantly increased in the xenograft tissues from cinobufagin group. Lymphocyte population of CD3+, CD4+, CD8+ were also elevated in xenograft tumors and adjacent tissues. In the cell co-culture assays, the content of β-END in the supernatant was significantly increased by cinobufagin in a dose-dependent manner. Cinobufagin also largely increased the proliferation of immune cells and inhibited H22 hepatoma carcinoma cell proliferation in single or co-culture cell assays. Gene expression of POMC and CTSL in cinobufagin group was significantly up-regulated comparing to the control group. Finally, cinobufagin addition enhanced the migration of immune cells in transwell assay.. Cinobufagin-induced local analgesic effect might be associated with increased activity of POMC/β-END/μ-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.

Topics: Analgesics; Animals; beta-Endorphin; Bufanolides; Carcinoma, Hepatocellular; Cell Line, Tumor; Coculture Techniques; Corticotropin-Releasing Hormone; Disease Models, Animal; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Female; Immunohistochemistry; Interleukin-1beta; Liver Neoplasms; Lymphocytes, Tumor-Infiltrating; Mice; Neoplasms, Experimental; Pain; Pain Threshold; Polymerase Chain Reaction; Random Allocation

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225μg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or μ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the β-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue.

Topics: Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents; beta-Endorphin; Caudate Nucleus; Drug Interactions; Interleukin-1beta; Male; Pain; Polysaccharides; Rats; Rats, Wistar; Receptors, Opioid; Seaweed; Sulfates; Temporomandibular Joint; Tumor Necrosis Factor-alpha

Personal social network size exhibits considerable variation in the human population and is associated with both physical and mental health status. Much of this inter-individual variation in human sociality remains unexplained from a biological perspective. According to the brain opioid theory of social attachment, binding of the neuropeptide β-endorphin to μ-opioid receptors in the central nervous system (CNS) is a key neurochemical mechanism involved in social bonding, particularly amongst primates. We hypothesise that a positive association exists between activity of the μ-opioid system and the number of social relationships that an individual maintains. Given the powerful analgesic properties of β-endorphin, we tested this hypothesis using pain tolerance as an assay for activation of the endogenous μ-opioid system. We show that a simple measure of pain tolerance correlates with social network size in humans. Our results are in line with previous studies suggesting that μ-opioid receptor signalling has been elaborated beyond its basic function of pain modulation to play an important role in managing our social encounters. The neuroplasticity of the μ-opioid system is of future research interest, especially with respect to psychiatric disorders associated with symptoms of social withdrawal and anhedonia, both of which are strongly modulated by endogenous opioids.

Topics: Adolescent; Adult; beta-Endorphin; Female; Humans; Male; Pain; Pain Threshold; Receptors, Opioid, mu; Social Support; Young Adult

This study was designed to investigate the contribution of prostaglandins to the maintenance of inflammatory pain. Inflammation was induced by intraplantar (i.pl.) injection of carrageenan in right hindpaw in rats. Indomethacin (non-selective COX inhibitor) was administered i.pl. 1 h after the carrageenan injection, and paw withdrawal latency (PWL) responding to noxious heat was measured. β-endorphin (β-END) and μ-opioid receptor (MOR) expressed in the inflamed site were examined by using immunocytochemistry, ELISA and RT-PCR techniques. The results showed that indomethacin dose-dependently increased PWL to the levels that were above the baseline on the day 2 and 3, referred to as hypoalgesia. The hypoalgesia was abolished by a local injection of the non-selective opioid receptor inhibitor naloxone methiodide. The number of β-END-positive cells, the content of β-END and the expression of MOR mRNA in the inflammatory site of inflammation model rats were all significantly increased by indomethacin. These results reveal a novel mechanism of prostaglandins for the inhibition of inflammation-induced endogenous opioid activity. This study provides further evidence that inhibition of prostaglandins in inflamed site could be a promising therapy for inflammatory pain.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Carrageenan; Indomethacin; Inflammation; Naloxone; Pain; Prostaglandins; Rats; Receptors, Opioid

Two peptide agonists of the glucagon-like peptide-1 (GLP-1) receptor, exenatide and GLP-1 itself, exert anti-hypersensitive effects in neuropathic, cancer and diabetic pain. In this study, we have assessed the anti-allodynic and anti-hyperalgesic effects of the non-peptide agonist WB4-24 in inflammatory nociception and the possible involvement of microglial β-endorphin and pro-inflammatory cytokines.. We used rat models of inflammatory nociception induced by formalin, carrageenan or complete Freund's adjuvant (CFA), to test mechanical allodynia and thermal hyperalgesia. Expression of β-endorphin and pro-inflammatory cytokines was measured using real-time quantitative PCR and fluorescent immunoassays.. WB4-24 displaced the specific binding of exendin (9-39) in microglia. Single intrathecal injection of WB4-24 (0.3, 1, 3, 10, 30 and 100 μg) exerted dose-dependent, specific, anti-hypersensitive effects in acute and chronic inflammatory nociception induced by formalin, carrageenan and CFA, with a maximal inhibition of 60-80%. Spinal WB4-24 was not effective in altering nociceptive pain. Subcutaneous injection of WB4-24 was also antinociceptive in CFA-treated rats. WB4-24 evoked β-endorphin release but did not inhibit expression of pro-inflammatory cytokines in either the spinal cord of CFA-treated rats or cultured microglia stimulated by LPS. WB4-24 anti-allodynia was prevented by a microglial inhibitor, β-endorphin antiserum and a μ-opioid receptor antagonist.. Our results suggest that WB4-24 inhibits inflammatory nociception by releasing analgesic β-endorphin rather than inhibiting the expression of proalgesic pro-inflammatory cytokines in spinal microglia, and that the spinal GLP-1 receptor is a potential target molecule for the treatment of pain hypersensitivity including inflammatory nociception.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; beta-Endorphin; Carrageenan; Cells, Cultured; Cyclobutanes; Formaldehyde; Freund's Adjuvant; Glucagon-Like Peptide-1 Receptor; HEK293 Cells; Hot Temperature; Humans; Hydrogen Peroxide; Hyperalgesia; Male; Microglia; Oxidants; Oxidative Stress; Pain; PC12 Cells; Rats; Rats, Wistar; Receptors, Glucagon; Spine

A disturbed beta-endorphin system can be a part of the post-traumatic stress disorder (PTSD) and depression allostasis. Study subjects (N=392) included those with PTSD and/or (stress-induced) depression, and healthy controls with and without traumas. The aim of the study was to examine the network of relations centered around plasma beta-endorphin. The network included anxiety (as a personality trait), traumatic events, pain, aggressiveness, depressive symptoms, and three clusters of PTSD symptoms: intrusions, avoidance, and hyperarousal. Beta-endorphin was represented by individual mean from 13 time points (BEmean), reflecting the total amount of the peripherally secreted hormone, and the coefficient of variation (BEvar), calculated as the ratio of standard deviation to the mean, reflecting the hormone׳s dynamics. BEvar correlated with all other variables, BEmean had no correlations. Structural equation modeling (SEM) was used to examine all interrelations (including their directions) of BEvar and the state/trait variables in the context of their entirety. The model revealed that hyperarousal and anxiety were the only direct agents of peripheral beta-endorphin fluctuations, mediating the effects of other variables. Traumatic events and intrusions act on BEvar via hyperarousal, while depressive symptoms, avoidance, and pain act via anxiety. Hyperarousal should be emphasized as the main agent not only because its effect on BEvar is larger than that of anxiety, but also because it increases anxiety itself (via avoidance and pain). All influences on BEvar are positive and they indicate long-term (sensitizing) effects (as opposed to direct stimulation, for example, by acute pain, anger, etc.). Relations apart from beta-endorphin are also discussed.

Topics: Adult; Aggression; Anxiety; beta-Endorphin; Biomarkers; Depression; Humans; Male; Models, Psychological; Pain; Stress Disorders, Post-Traumatic; Wounds and Injuries; Young Adult

How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, β-endorphin (10-100 nmol) and GRP (1-10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike β-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100-1000 nmol) and nociceptin-orphanin FQ (3-30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1-17) (10-100 nmol) dose-dependently attenuates both β-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by β-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; beta-Endorphin; Dynorphins; Female; Gastrin-Releasing Peptide; Hyperalgesia; Injections, Spinal; Macaca mulatta; Male; Neuropeptides; Pain; Pruritus; Spinal Cord

Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect.. The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2μg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of β-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws.. Intraplantar injection of kahweol (40 and 80μg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100μg/paw) prevented action of kahweol (80μg/paw) and the aminopeptidases inhibitor bestatin (400μg/paw) potentiated the antinociceptive effect of kahweol (40μg/paw). Furthermore, kahweol treatment increased the intensity of β-endorphin immunoreactivity in the epithelium of rat paws.. The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

Topics: Analgesics; Animals; beta-Endorphin; Coffee; Dinoprostone; Diterpenes; Hyperalgesia; Leucine; Male; Naloxone; Narcotic Antagonists; Opioid Peptides; Pain; Pain Measurement; Peptides; Pressure; Rats; Rats, Wistar; Skin

This study quantified the expression of substance P (SP), calcitonin gene-related peptide (CGRP), β-endorphins (β-End), and methionine-enkephalin (Met-Enk) in human dental pulp following orthodontic intrusion.. Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons) were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg), which would undergo controlled intrusive force for seven days, and the control group (CTRg), which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA).. All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg.. SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain.

Topics: Adolescent; Analgesics, Opioid; beta-Endorphin; Calcitonin Gene-Related Peptide; Child; Dental Pulp; Enkephalins; Female; Humans; Inflammation; Male; Methionine; Molar; Neuropeptides; Orthodontics; Pain; Pilot Projects; Radioimmunoassay; Substance P

Less than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long-term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety- and stress-provoking stimuli. These long-term changes in pain and stress responsiveness are accompanied by two-fold increases in central met-enkephalin and β-endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met-enkephalin and β-endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met-enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain β-endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post-injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury-induced changes become programmed and permanent.

Topics: Animals; Animals, Newborn; beta-Endorphin; Biomarkers; Brain Chemistry; Carrageenan; Corticosterone; Enkephalin, Methionine; Female; Inflammation; Pain; Pregnancy; Rats; Rats, Sprague-Dawley; Spinal Cord; Stress, Psychological

To measure the plasma concentrations of three endogenous opioid peptides and the levels of preproenkephalin (PPE) and preprodynorphin (PPD) mRNA in peripheral blood lymphocytes of patients during scheduled surgery performed under intravenous general anaesthesia combined with an epidural block.. Patients were anaesthetized and arterial blood was collected at 0 (baseline), 20, 40, 60, and 80 min during surgery. The plasma concentrations of β-endorphin, leucine-enkephalin and dynorphin A were measured using radioimmunoassay. Reverse transcription-polymerase chain reaction was used to measure the levels of PPD and PPE mRNA in peripheral blood lymphocytes collected during surgery.. Fifteen patients participated in this prospective study. The plasma concentrations of β-endorphin were significantly lower at all time-points compared with the baseline value. The plasma concentrations of leucine-enkephalin and dynorphin A were significantly lower at 40, 60, and 80 min compared with baseline. The PPD/β-actin ratio was significantly lower at 80 min compared with baseline, while the PPE/β-actin ratio showed no significant change.. The level of mRNA from two pre-endogenous opioid peptide genes either decreased or remained unchanged during surgery under intravenous general anaesthesia with epidural block, suggesting that patients remained pain free during surgery.

Topics: Abdomen; Adult; Anesthesia, Epidural; Anesthesia, General; Anesthetics, Intravenous; beta-Endorphin; Bupivacaine; Dynorphins; Enkephalin, Leucine; Enkephalins; Female; Fentanyl; Gene Expression; Humans; Male; Midazolam; Middle Aged; Pain; Prospective Studies; Protein Precursors; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vecuronium Bromide

Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the μ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide β-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls.. The plasma β-endorphin levels were significantly higher in controls than in pain patients.A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found.. Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.

Topics: Adult; Aged; Analgesics, Opioid; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; beta-Endorphin; Calcium Channels; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Pain; Polymorphism, Single Nucleotide; Quality of Life; Receptors, Opioid, mu

The gut is a major site of contact between immune and sensory systems and evidence suggests that patients with irritable bowel syndrome (IBS) have immune dysfunction. Here we show how this dysfunction differs between major IBS subgroups and how immunocytes communicate with sensory nerves.. Peripheral blood mononuclear cell supernatants from 20 diarrhoea predominant IBS (D-IBS) patients, 15 constipation predominant IBS (C-IBS) patients and 36 healthy subjects were applied to mouse colonic sensory nerves and effects on mechanosensitivity assessed. Cytokine/chemokine concentration in the supernatants was assessed by proteomic analysis and correlated with abdominal symptoms, and expression of cytokine receptors evaluated in colonic dorsal root ganglia neurons. We then determined the effects of specific cytokines on colonic afferents.. D-IBS supernatants caused mechanical hypersensitivity of mouse colonic afferent endings, which was reduced by infliximab. C-IBS supernatants did not, but occasionally elevated basal discharge. Supernatants of healthy subjects inhibited afferent mechanosensitivity via an opioidergic mechanism. Several cytokines were elevated in IBS supernatants, and levels correlated with pain frequency and intensity in patients. Visceral afferents expressed receptors for four cytokines: IL-1β, IL-6, IL-10 and TNF-α. TNF-α most effectively caused mechanical hypersensitivity which was blocked by a transient receptor potential channel TRPA1 antagonist. IL-1β elevated basal firing, and this was lost after tetrodotoxin blockade of sodium channels.. Distinct patterns of immune dysfunction and interaction with sensory pathways occur in different patient groups and through different intracellular pathways. Our results indicate IBS patient subgroups would benefit from selective targeting of the immune system.

Topics: Adult; Animals; beta-Endorphin; Case-Control Studies; Cells, Cultured; Colon; Constipation; Culture Media, Conditioned; Cytokines; Diarrhea; Female; Ganglia, Spinal; Humans; Irritable Bowel Syndrome; Leukocytes, Mononuclear; Male; Mice; Middle Aged; Neuroimmunomodulation; Neurons, Afferent; Pain; Receptors, Cytokine

We have recently reported that treatment with the 5-HT(2A) receptor antagonist ketanserin in the inflamed paw raises the nociceptive threshold above normal level (hypoalgesia) and this response is naloxone-reversible. The present study aimed to investigate neurochemical changes at the site of inflammation and in dorsal root ganglia (DRG) and the spinal cord following the blockade of 5-HT(2A) receptors. Intraplantar injection of ketanserin (20 μg) inhibited carrageenan-induced increase in CGRP immunoreactivity-positive neurons in DRG. On the other hand, administration of ketanserin (20 μg) and 5-HT (10 μg), but not vehicle, enhanced and inhibited recruitment of β-endorphin-expressing immune cells, respectively, in subcutaneous loci of inflamed hindpaw. Moreover, the treatment with ketanserin increased the number of endomorphine-containing cells in the inflamed paw and μ-opioid receptor-expressing neurons in DRG at L4-5 but reduced the expression of endomorphine in superficial layers of the lumbar spinal cord. The present study provided evidence at the cellular level showing that the blockade of 5-HT(2A) receptors inhibited inflammation-associated increase in pronociceptive mediator, and that the pronociceptive property of 5-HT is mediated by the suppression of inflammation-activated opioid mechanism. Therefore, targeting the 5-HT(2A) receptors in the site of inflammation may be a promising approach to inhibit inflammatory pain.

Topics: Animals; beta-Endorphin; Calcitonin Gene-Related Peptide; Carrageenan; Ganglia, Spinal; Inflammation; Ketanserin; Male; Pain; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, Opioid, mu; Serotonin; Serotonin 5-HT2 Receptor Antagonists; Spinal Cord

We have evaluated the possible underlying mechanisms of immobilization stress-induced analgesia (SIA) by behavioral cross-tolerance studies and molecular studies. In the behavioral studies, the cross-tolerance between single or repeated immobilization SIA and the antinociceptive effects of β-endorphin, morphine, 5-hydroxytryptamine (5-HT), or WIN55,212-2 were assessed. Both single and repeated (×7) immobilization stress significantly attenuated the β-endorphin and 5-hydroxytryptamine-induced antinociception in the 2nd phase of formalin response, respectively. However, these cross-tolerances disappeared in prolonged repetition of the stress (×14). Neither single nor repeated (×7 and ×14) immobilization stress affected the antinociceptive effect of morphine or WIN55,212-2 at all. We also found that immobilization stress activated hypothalamic proopiomelanocortin (POMC) gene and β-endorphin expression. Since, it has potent inhibitory activity on the noxious stimuli-induced POMC expression, immobilization stress seemed to dissipate the POMC gene expression process. Meanwhile, we did not find any changes in the opioid receptors' (mu-, delta- and kappa-receptor) and the cannabinoid receptors' (CB1 and CB2) expressions in the midbrain regions elicited by single or repeated stress. These results suggested that a single immobilization stress activates the descending pain modulatory system, which is mainly mediated through endorphinergic and serotonergic activation. Moreover, the tolerance of SIA induced by repeated stresses may be due to the prolonged activation of these systems induced by repeated immobilization.

Topics: Analgesics; Animals; Benzoxazines; beta-Endorphin; Disease Models, Animal; Inflammation; Infusions, Intraventricular; Male; Mice; Mice, Inbred ICR; Morphine; Morpholines; Naphthalenes; Pain; Receptors, Cannabinoid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Restraint, Physical; Serotonin; Stress, Physiological; Stress, Psychological

Periaqueductal gray (PAG) plays a very important role in pain modulation through endogenous opiate peptides including leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), β-endorphin (β-Ep) and dynorphin A(1-13) (DynA(1-13)). Our pervious study has demonstrated that intra-PAG injection of oxytocin (OXT) increases the pain threshold, and local administration of OXT receptor antagonist decreases the pain threshold, in which the antinociceptive role of OXT can be reversed by pre-PAG administration of OXT receptor antagonist. The experiment was designed to investigate the effect of OXT on endogenous opiate peptides in the rat PAG during the pain process. The results showed that (1) the concentrations of OXT, L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased after the pain stimulation; (2) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were decreased by the OXT receptor antagonist; (3) the increased pain threshold induced by the OXT was attenuated by naloxone, an opiate receptor antagonist; and (4) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased by exogenous OXT administration. The data suggested that OXT in the PAG could influence the L-Ek, M-Ek and β-Ep rather than DynA(1-13) to participate in pain modulation, i.e. OXT in the PAG participate in pain modulation by influencing the L-Ek, M-Ek and β-Ep rather than DynA(1-13).

Topics: Animals; beta-Endorphin; Catheterization; Dynorphins; Enkephalin, Leucine; Enkephalin, Methionine; Microinjections; Naloxone; Narcotic Antagonists; Oxytocin; Pain; Pain Measurement; Pain Threshold; Peptide Fragments; Periaqueductal Gray; Radioimmunoassay; Rats; Rats, Sprague-Dawley

We have previously demonstrated that the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has an antinociceptive effect on various pain stimuli in a naloxone-reversible manner. In the present study, the role of the endogenous opioid peptide β-endorphin in DHA-induced antinociception was examined. DHA-induced antinociception was abolished when mice were pretreated with the μ-opioid receptor antagonist β-funaltrexamine (β-FNA) and the δ-opioid receptor antagonist naltrindole, but not by the κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) in the acetic acid-induced writhing test. In the radioligand binding assay, DHA itself did not have affinity for μ- , δ- or κ-opioid receptors. On the other hand, the pretreatment of anti-β-endorphin antiserum inhibited DHA-induced antinociception. Furthermore, the intracerebroventricular injection of DHA dose-dependently reduced writhing behavior, and this effect was inhibited by d-Phe-Cys-Tyr-Orn-Thr-Pen-Thr-NH(2) (CTOP) and naltrindole, but not nor-BNI. β-endorphin-induced antinociception was inhibited by the pretreatment of β-FNA, but not naltrindole or nor-BNI, and its levels in plasma were increased by DHA treatment. These findings suggest that the induction of antinociception by DHA may partially involve the μ-opioid receptor via the release of β-endorphin.

Topics: Acetic Acid; Analgesics; Animals; Behavior, Animal; beta-Endorphin; Docosahexaenoic Acids; Male; Mice; Narcotic Antagonists; Pain; Receptors, Opioid; Time Factors

A prospective observational study was performed to evaluate whether the plasma concentration of heat shock protein 72 (HSP72) or beta-endorphin is related to clinical signs, blood chemistry, or severity of pain of colic. Seventy-seven horses with colic and 15 clinically healthy controls were studied. The horses were divided into four groups which reflected increasing severity of colic, from normal control horses to horses with mild, moderate and severe colic. Blood samples were collected before any treatment. Packed cell volume (PCV) and plasma HSP72, beta-endorphin, cortisol, adrenocorticotropic hormone (ACTH) and lactate concentrations were measured. Plasma beta-endorphin was related with severity of colic and survival, as well as with plasma cortisol, ACTH and lactate concentrations, heart rate, PCV and pain score. High plasma HSP72 concentration may indicate circulatory deficits, but was not associated with clinical signs of colic. Plasma lactate still seemed to be the most useful single prognostic parameter in horses with colic.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Biomarkers; Blood Chemical Analysis; Case-Control Studies; Colic; Female; Horse Diseases; Horses; HSP72 Heat-Shock Proteins; Hydrocortisone; Lactic Acid; Male; Pain; Prognosis; Prospective Studies; Severity of Illness Index

Peptide E (a 25-amino acid peptide derived from proenkephalin A) and beta-endorphin (a 31-amino acid peptide derived from proopiomelanocortin) bind with high affinity to opioid receptors and share structural similarities but induce analgesic effects of very different intensity. Indeed, whereas they possess the same N-terminus Met-enkephalin message sequence linked to a helix by a flexible spacer and a C-terminal part in random coil conformation, in contrast with peptide E, beta-endorphin produces a profound analgesia. To determine the key structural elements explaining this very divergent opioid activity, we have compared the structural and pharmacological characteristics of several chimeric peptides derived from peptide E and beta-endorphin. Structures were obtained under the same experimental conditions using circular dichroism, computational estimation of helical content and/or nuclear magnetic resonance spectroscopy (NMR) and NMR-restrained molecular modeling. The hot-plate and writhing tests were used in mice to evaluate the antinociceptive effects of the peptides. Our results indicate that neither the length nor the physicochemical profile of the spacer plays a fundamental role in analgesia. On the other hand, while the functional importance of the helix cannot be excluded, the last 5 residues in the C-terminal part seem to be crucial for the expression or absence of the analgesic activity of these peptides. These data raise the question of the true function of peptides E in opioidergic systems.

Topics: Amino Acid Motifs; Amino Acid Sequence; Analgesics; Animals; beta-Endorphin; Circular Dichroism; Enkephalins; Magnetic Resonance Spectroscopy; Male; Mice; Molecular Sequence Data; Pain; Peptides; Structure-Activity Relationship

Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment.

Topics: Animals; beta-Endorphin; Cell Line, Tumor; Disease Models, Animal; Down-Regulation; Endothelin-1; Endothelins; Humans; Mice; Mice, Nude; Narcotic Antagonists; Neoplasm Transplantation; Neoplasms; Nociceptors; Oligopeptides; Opioid Peptides; Pain; Peptide Fragments; Piperidines; Receptor, Endothelin B; Receptors, Opioid; Sensory Receptor Cells; Up-Regulation

Hyperbaric oxygen (HBO(2)) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO(2) treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO(2)-induced antinociception was significantly attenuated by pretreatment before HBO(2) exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl-L-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N(5)-(1-iminoethyl)-L-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin(1-13) but not by rabbit antisera against either beta-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO(2)-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO(2) treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO(2) exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO(2) treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO(2) may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect.. This article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems.

Topics: Acetic Acid; Analgesia; Analysis of Variance; Animals; beta-Endorphin; Citrulline; Dynorphins; Enkephalin, Methionine; Enzyme Inhibitors; Hyperbaric Oxygenation; Injections, Intraperitoneal; Male; Mice; Microinjections; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pain; Pain Measurement; Thiourea

The timing of the measurement of biological samples (e.g. biomarkers) is not always standardized. Biomarkers are the focus of many recent studies and treatments. The purpose of this study was to determine the timing of the release of beta-endorphin (BE), a possible biomarker, after exposure to pain and/or handling stress in order to standardize measurements. Mouse plasma was collected for BE analysis following handling i.e. being picked up by the investigator, exposure to a painful (55 degrees C hot-plate), or exposure to a nonpainful stimulus (room temperature hot-plate). The groups exposed to either a painful or nonpainful stimulus released BE in response to the stimulus, but the duration of the response was longer in mice exposed to a painful stimulus than in mice exposed to a nonpainful stimulus. The BE in the mice exposed to a nonpainful stimulus peaked at 1 min and returned to baseline levels by 5 min while the BE response of the mice exposed to a painful stimulus peaked at 10 min and remained elevated for 25 min. The results of this study indicate that BE can be a biomarker for pain and handling stress, however, the timing of the measurement should differ.

Topics: Acute Disease; Animals; beta-Endorphin; Biomarkers; Disease Models, Animal; Male; Mice; Mice, Inbred DBA; Neurochemistry; Pain; Pain Measurement; Physical Stimulation; Radioimmunoassay; Reproducibility of Results; Time Factors; Up-Regulation

Although N-methyl-d-aspartate (NMDA) receptor antagonists potentiate antinociceptive effects induced by various exogenous opioids at the spinal, supraspinal, or peripheral level, less is known regarding the interaction between NMDA and endogenous opioids in antinociception. We therefore assessed the effects of NMDA receptor antagonists on endogenous opioids in antinociception at the peripheral level by testing the ability of the locally administered receptor antagonists to modify pain-related behavior induced by carrageenan injection into the knee joint. The NMDA receptor antagonist AP-5 or the exogenous opioid morphine was injected intra-articularly before carrageenan injection and 5h after carrageenan injection, respectively. We evaluated whether intra-articular injection of the opioid receptor antagonist naloxone reversed the analgesic effect of AP-5. In addition, we tested the effects of AP-5 on carrageenan-induced levels of the beta-endorphin protein in dorsal root ganglia (DRG), saphenous nerve and synovial membrane. We found that AP-5 prevented and morphine reversed carrageenan-induced pain-related behavior. Intriguingly, injection of naloxone 5h after carrageenan injection reversed the antinociceptive effects of AP-5 pre-treatment, although naloxone alone had no effect on carrageenan-induced pain-related behavior. Western blots showed that AP-5 pre-treatment followed by carrageenan injection resulted in a higher level of beta-endorphin protein in the DRG and saphenous nerve, but not in the synovial membrane, than that observed following saline control treatment. These results suggest that inhibition of the NMDA receptor unmasks antinociception induced by endogenous opioids at the peripheral level, partly through the increased protein level of the endogenous mu-opioid peptide beta-endorphin in DRG and saphenous nerve.

Topics: 2-Amino-5-phosphonovalerate; Analgesics, Opioid; Animals; Arthralgia; Arthritis; beta-Endorphin; Carrageenan; Drug Synergism; Excitatory Amino Acid Antagonists; Ganglia, Spinal; Male; Morphine; Naloxone; Narcotic Antagonists; Opioid Peptides; Pain; Pain Measurement; Pain Threshold; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Synovial Membrane

Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma beta-endorphin levels and their relationship in a large group of individuals with autism.. The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma beta-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Delta heart rate) was significantly greater than for controls (mean+/-SEM; 6.4+/-2.5 vs. 1.3+/-0.8 beats/min, P<0.05). Plasma beta-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity.. The greater heart rate response to venepuncture and the elevated plasma beta-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain.

Topics: Adolescent; Autistic Disorder; beta-Endorphin; Case-Control Studies; Child; Female; Humans; Male; Pain

Cancer pain impairs the quality of life of cancer patients, but opioid analgesics can not only cause inhibition of respiratory function, and constipation, but also other significant side effects such as addiction and tolerance that further decrease quality of life. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in cancer pain mouse model. In order to induce neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. The mass of S-180 cancer cells embedded around sciatic nerve in a time course was confirmed by Magnetic Resonance Imaging (MRI) scanning. Mechanical allodynia was most consistently induced in mouse sarcoma cell line S-180 (2 x 10(6) sarcoma cells) treated group among all groups. EA stimulation (2Hz) was daily given to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation. EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation as well as shortened cumulative lifting duration from 7 days after inoculation compared with tumor control. In addition, the overexpressions of pain peptide substance P in dorsal horn of spinal cord were significantly decreased in EA treated group compared with tumor control on Day 9 after inoculation. Furthermore, EA treatment effectively increased the concentration of beta endorphin in blood and brain of mice more than tumor control as well as normal group. The concentration of beta-endorphin for EA treatment group increased by 51.457% in blood 12.6% in brain respectively, compared with tumor control group. These findings suggest that S-180 cancer pain model can be a consistent and short time animal model and also EA treatment can be an alternative therapeutic method for cancer pain via decreased substance P and increased beta endorphin.

Topics: Acupuncture Analgesia; Acupuncture Points; Animals; beta-Endorphin; Cell Line, Tumor; Disease Models, Animal; Electroacupuncture; Humans; Male; Mice; Mice, Inbred BALB C; Neoplasms; Pain; Pain Management; Pain Threshold; Substance P

The effect of proopiomelanocortin (POMC) gene transfer with radial shock waves (RSW) was investigated in vitro and in vivo rat pain models.. To examine the efficacy of POMC gene transfer with RSW, efficiency of beta-endorphin production in transfected cells, and its effects and side effects in pain models.. Opioids have been used to treat chronic pain originating from knee osteoarthritis and the lower back; however, several side effects have been reported. Endogenous opioids are safe, but they are not used for clinical treatment because their metabolism is very fast.. POMC plasmid was produced from pretransformed rat brain cDNA. POMC gene was added to the muscle of rat in vitro and in vivo with RSWs. We assessed beta-endorphin activity using immunohistochemistry. For assessment of pain behavior, we evaluated change in pain score and the level of the inflammatory neuropeptide, calcitonin gene-related peptide (CGRP), after transfection of the POMC gene in an adjuvant induced pain model for 28 days after treatment.. POMC transfected using RSW expressed beta-endorphin at a significantly increased level in muscle cells compared with non-RSW transfection and controls in vitro and in vivo (P < 0.05).Animals showed significant pain sensitivity and increased CGRP expression in dorsal root ganglia neurons in this model; however, these findings decreased for 14 days after transfection of POMC into muscle. There was no significant difference in side effects, such as a change in the level of food pellet intake or constipation, between POMC-treated animals and untreated animals.. POMC transfection with RSW increased beta-endorphin expression in muscle for 14 days, and suppressed pain behavior and CGRP expression in dorsal root ganglia neurons without side effects. This suggested that transfer of POMC by RSW is an effective treatment for inflammatory pain.

Topics: Animals; Behavior, Animal; beta-Endorphin; Buttocks; Calcitonin Gene-Related Peptide; Cells, Cultured; Ganglia, Spinal; High-Energy Shock Waves; In Vitro Techniques; Muscle, Skeletal; Myositis; Pain; Pain Measurement; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; Transfection; Up-Regulation

It is well established that African Americans (AA) experience greater pain associated with a variety of clinical conditions, and greater pain sensitivity to experimental pain tasks relative to non-Hispanic Whites (W). Notably, African Americans do not show the same relationships involving endogenous pain regulatory mechanisms and pain sensitivity documented in Caucasians, including positive associations between blood pressure, norepinephrine, cortisol and greater pain tolerance.. The purpose of this study was to examine the relationship between plasma oxytocin (OT) and pain sensitivity and to explore the relation of OT to other factors known to influence pain perception.. OT concentration and sensitivity to ischemic, cold pressor, and thermal pain tasks were assessed in African American (n=25) and non-Hispanic White (n=23) pre-menopausal women.. African American women demonstrated significantly lower pain tolerance across tasks compared with Whites (F(1,46)=6.31, p=0.0156) and also exhibited lower plasma OT levels (AA: 3.90, W: 7.05 pg/mL; p=0.0014). Greater OT levels were correlated with greater tolerance to ischemic pain (r=0.36, p=0.013) and accounted for a marginally significant portion of the ethnic difference in ischemic pain tolerance (B=+0.29, p=0.06). Greater OT was also correlated with greater tolerance of cold pressor pain (r=0.31, p=0.03); however, this association was no longer seen after the variance due to ethnicity was accounted for.. These data suggest that reduced oxytocinergic function may be one of multiple biological factors contributing to the greater sensitivity to experimental ischemic pain, and to the greater burden of some types of clinical pain experienced by African Americans compared with Whites.

Topics: Adult; beta-Endorphin; Black or African American; Female; Humans; Norepinephrine; Oxytocin; Pain; Pain Threshold; Surveys and Questionnaires; White People

To determine the effectiveness of two long-acting non-steroidal anti-inflammatory drugs (NSAIDs) at reducing the pain and stress responses to mulesing in lambs.. Merino lambs (n = 60) were allocated at 5 weeks of age to six treatment groups: (1) sham mules; (2) mules; (3) tolfenamic acid-sham mules; (4) tolfenamic acid administered 45 min before mulesing; (5) tolfenamic acid at the time of mulesing; (6) meloxicam at the time of mulesing. Plasma cortisol was measured at -0.75, -0.25, 0, 0.5, 1, 3, 6, 12, 24, 48 and 72 h relative to mulesing. Beta-endorphin concentrations in plasma were determined at 0, 0.5, 1, 6, 12, 24, and 48 h. Haematology was performed on blood samples taken at -0.75, 0, 24, 48 and 72 h. Plasma haptoglobin was measured at 0, 12, 24, 48 and 72 h. Rate of wound healing was determined 72 h post mulesing, and animal behaviour, including posture, was measured for 6 h after mulesing.. The mulesed lambs exhibited large increases in plasma concentrations of cortisol, beta-endorphin and haptoglobin. All mulesed animals lost weight significantly in the week after mulesing, regardless of analgesic administration, but the difference in weight between mulesed and unmulesed lambs was less at the final measurement, 2 weeks after mulesing. Mulesed lambs spent significantly less time lying ventrally than control lambs. All lambs that were mulesed, including those administered NSAIDs, spent more time standing with a hunched posture and less time walking normally than control lambs.. The NSAID treatments applied 45 min before or at the time of mulesing at the dose levels used in this study were not effective in reducing the acute response of lambs to mulesing.

Topics: Analgesics; Animal Welfare; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; beta-Endorphin; Female; Haptoglobins; Hydrocortisone; Male; Meloxicam; ortho-Aminobenzoates; Pain; Posture; Random Allocation; Sheep; Sheep Diseases; Thiazines; Thiazoles; Time Factors; Treatment Outcome; Wound Healing

Low-level laser therapy (LLLT) has been reported to relieve pain, free of side effects. However, the mechanisms underlying LLLT are not well understood. Recent studies have also demonstrated that opioid-containing immune cells migrate to inflamed sites and release beta-endorphins to inhibit pain as a mode of peripheral endogenous opioid analgesia. We investigated whether pre-irradiation of blood by LLLT enhances peripheral endogenous opioid analgesia.. The effect of LLLT pretreatment of blood on peripheral endogenous opioid analgesia was evaluated in a rat model of inflammation. Additionally, the effect of LLLT on opioid production was also investigated in vitro in rat blood cells. The expression of the beta-endorphin precursors, proopiomelanocortin and corticotrophin releasing factor, were investigated by reverse transcription polymerase chain reaction.. LLLT pretreatment produced an analgesic effect in inflamed peripheral tissue, which was transiently antagonized by naloxone. Correspondingly, beta-endorphin precursor mRNA expression increased with LLLT, both in vivo and in vitro.. These findings suggest that that LLLT pretreatment of blood induces analgesia in rats by enhancing peripheral endogenous opioid production, in addition to previously reported mechanisms.

Topics: Adjuvants, Immunologic; Aluminum; Analgesics, Opioid; Animals; Arsenicals; beta-Endorphin; Blood; Gallium; Immunohistochemistry; Inflammation; Lasers; Male; Models, Biological; Pain; Rats; Rats, Sprague-Dawley

To probe into the best parameter of electroacupuncture (EA) for treatment of inflammatory pain in the rat.. One hundred and twenty Wistar rats were randomly divided into 12 groups, normal control group, model group and 10 EA groups including A1 B1 C1, A1 B1 C2, A1 B2 C1, A1 B2 C2, A2 B1 C1, A2 B1 C2, A2 B2 C1, A2 B2 C2 (A1 : 2 Hz, A2: 100 Hz; B1 : successive wave; B2: intermittent wave; C1: 0.1 mA, C2: 0.2 mA), A3 B3 C1 (4/20 Hz, disperse-dense wave, 0.1 mA) and A3 B3 C2 (4/20 Hz, disperse-dense wave, 0.2 mA). The rats of adjuvant-induced arthritis in all of the EA groups were treated by EA with selected different parameters once every day for 6 days. Pain thresholds and beta-endorphin (beta-EP) content in the local tissue of inflammation were used as indexes to compare analgesic effects of EA of different frequencies, waveforms and currents by orthogonal experiment design and other methods.. The optimized parameters of raising the pain threshold was: 100 Hz, 0.1 mA, intermittent wave. EA at 100 Hz was better than 2 Hz for increasing the content of beta-EP in local tissue of inflammation. The analgesic effect of EA at 4/20 Hz, 0.1 mA, disperse-dense wave on the inflammatory pain in the rat was not significant different with that at 100 Hz, 0.1 mA, intermittent wave (P > 0.05).. The best parameters are 100 Hz, 0.1 mA and intermittent wave for EA treatment of inflammatory pain in the rat.

Topics: Acupuncture Analgesia; Animals; Arthritis; beta-Endorphin; Electroacupuncture; Female; Humans; Pain; Pain Management; Pain Threshold; Random Allocation; Rats; Rats, Wistar

Endorphins (EPs) present in human colostrum may be relevant for immediate postnatal fetal adaptation because this compound is involved in stress response and adaptation mechanisms. Endorphin levels in human colostrum are two-fold greater than corresponding maternal plasma levels; however, the high endorphin levels in human milk decrease as lactation continues. The aim of this study was to determine the beta-EP concentration in colostrums of women residing in Burkina Faso and Sicily. In addition, we investigated the source of potential differences in beta-EP levels between these populations, especially ethnic sources of these deviations.. The concentration of beta-EP was determined in the colostrum from the first 3 d subsequent to delivery by an enzyme immunoassay as immunoreactive material (IRM).. The production of beta-EP in the colostrum was significantly higher in Burkinabe mothers (0.83 +/- 0.04 ng/mL) than in Sicilian mothers (0.31 +/- 0.02 ng/mL) at 24 h after delivery. Colostrum levels of beta-EP declined progressively during the first 3 d after delivery in both populations (0.64 +/- 0.1 and 0.28 +/- 0.015 ng/mL, respectively, at 72 h). The level of beta-EP-IRM correlated significantly with pain and psychological involvement during and after delivery. In addition, the correlation between beta-EP-IRM and length of stage II of labor was significant (P < 0.0001) in the colostrums of Sicilian mothers who received ergot derivatives, episiorrhaphy, and child birth preparation. The correlation between beta-EP-IRM and length of stage II was less significant (P < 0.001) in the colostrums of Burkinabe mothers who received neither ergot derivatives nor child birth preparation.. During the first 3 d after labor the beta-EP-IRM concentration in the colostrums of Burkinabe mothers differs from that of Sicilians. In addition, because Burkinabe women produce a larger volume of colostrum, their newborns receive, during the first days of life, a larger absolute amount of beta-EP-IRM, likely resulting in better postnatal fetal adaptation.

Topics: Adaptation, Physiological; Adult; Analgesics, Non-Narcotic; beta-Endorphin; Burkina Faso; Colostrum; Ergotamine; Ethnicity; Female; Humans; Infant, Newborn; Italy; Labor Stage, Second; Lactation; Milk, Human; Pain; Postpartum Period; Pregnancy; Time Factors

Lumbar puncture (LP) is an attractive route to deliver drugs to the nervous system because it is a safe bedside procedure. Its use for gene therapy has been complicated by poor vector performance and failure to target neurons. Here we report highly effective gene transfer to the primary sensory neurons of the dorsal root ganglia (DRGs) with self-complementary recombinant adeno-associated virus serotype 8 (sc-rAAV8) modeling an LP. Transgene expression was selective for these neurons outlining their cell bodies in the DRGs and their axons projecting into the spinal cord. Immunohistochemical studies demonstrated transduction of cells positive for the nociceptive neuron marker vanilloid receptor subtype 1, the small peptidergic neuron markers substance P and calcitonin gene-related peptide, and the nonpeptidergic neuron marker griffonia simplicifolia isolectin B4. We tested the efficacy of the approach in a rat model of chronic neuropathic pain. A single administration of sc-rAAV8 expressing the analgesic gene prepro-beta-endorphin (ppbetaEP) led to significant (P < 0.0001) reversal of mechanical allodynia for >/=3 months. The antiallodynic effect could be reversed by the mu-opioid antagonist naloxone 4 months after gene transfer (P < 0.001). Testing of an alternative nonopioid analgesic gene, IL-10, alone or in combination with ppbetaEP was equally effective (P < 0.0001). All aspects of the procedure, such as the use of an atraumatic injection technique, isotonic diluent, a low-infusion pressure, and a small injection volume, are consistent with clinical practice of intrathecal drug use. Therefore, gene transfer by LP may be suitable for developing gene therapy-based treatments for chronic pain.

Topics: Animals; beta-Endorphin; Chronic Disease; Dependovirus; Disease Models, Animal; Genetic Therapy; Genetic Vectors; Immunohistochemistry; Kinetics; Male; Neurons, Afferent; Pain; Pain Management; Peripheral Nervous System Diseases; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Spinal Puncture

Although opioids are highly effective analgesics, they are also known to induce cellular adaptations resulting in tolerance. Experimental studies are often performed in the absence of painful tissue injury, which precludes extrapolation to the clinical situation. Here we show that rats with chronic morphine treatment do not develop signs of tolerance at peripheral mu-opioid receptors (micro-receptors) in the presence of painful CFA-induced paw inflammation. In sensory neurons of these animals, internalization of mu-receptors was significantly increased and G protein coupling of mu-receptors as well as inhibition of cAMP accumulation were preserved. Opioid receptor trafficking and signaling were reduced, and tolerance was restored when endogenous opioid peptides in inflamed tissue were removed by antibodies or by depleting opioid-producing granulocytes, monocytes, and lymphocytes with cyclophosphamide (CTX). Our data indicate that the continuous availability of endogenous opioids in inflamed tissue increases recycling and preserves signaling of mu-receptors in sensory neurons, thereby counteracting the development of peripheral opioid tolerance. These findings infer that the use of peripherally acting opioids for the prolonged treatment of inflammatory pain associated with diseases such as chronic arthritis, inflammatory neuropathy, or cancer, is not necessarily accompanied by opioid tolerance.

Topics: Animals; beta-Endorphin; Cells, Cultured; Cyclophosphamide; Drug Tolerance; Fentanyl; Guanosine 5'-O-(3-Thiotriphosphate); Inflammation; Male; Morphine; Neurons, Afferent; Pain; Rats; Rats, Wistar; Receptors, Opioid, mu

It has often been proposed that opioid addiction does not arise as a consequence of opioid treatment for pain. Recently, we demonstrated that activated protein kinase C (PKC) in the spinal cord associated with chronic pain-like hyperalgesia suppressed the morphine-induced rewarding effect in mice. In the present study, we investigated whether a gene deletion for an endogenous mu-opioid peptide beta-endorphin could affect pain-like behavior and the suppression of the morphine-induced rewarding effect by the direct activation of PKC in the spinal cord. We found that activation of spinal PKC by intrathecal (i.t.) treatment with phorbol 12,13-dibutyrate (PDBu), a specific PKC activator, caused thermal hyperalgesia, pain-like behaviors and suppression of the morphine-induced rewarding effect. This suppression of morphine reward was eliminated in mice that lacked beta-endorphin. In contrast, thermal hyperalgesia and pain-like behaviors were not affected in beta-endorphin knockout mice. These results suggest that the activation of PKC in the spinal cord may play an essential role in the suppression of the morphine-induced rewarding effect in mice with neuropathic pain through the constant release of beta-endorphin.

Topics: Animals; beta-Endorphin; Brain; Enzyme Activation; Enzyme Activators; Female; Hyperalgesia; Injections, Spinal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphine; Morphine Dependence; Narcotics; Neural Inhibition; Pain; Protein Kinase C; Reward; Spinal Cord

We examined proopiomelanocortin (POMC) mRNA and beta-endorphin expression in the hypothalamus of mice after various nociceptive stimuli. The time-course study (10 min, 30 min, 1 h, 2 h, and 10 h) showed that the POMC mRNA level significantly increases from 1 h after s.c. formalin injection and returns to the control level at 10 h. Intrathecal (i.t.) substance P (SP) injection also increases the hypothalamic POMC mRNA level from 1 h to 10 h. However, i.t. glutamate injection did not affect the hypothalamic POMC gene expression at all time points. We found that the POMC mRNA after s.c. formalin injection was located in the arcuate nucleus of the hypothalamus. In the same manner, beta-endorphin immunoreactivity was also increased in the hypothalamic arcuate nucleus. The expression of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2), phosphorylated calcium/calmodulin-dependent protein kinase-IIalpha (pCaMK-IIalpha) protein and phosphorylated IkappaB (pIkappaB) protein was increased by s.c. formalin injection at various time points. We also found that increased pERK1/2, pCaMKIIalpha and pIkappaB protein after s.c. formalin injection was mainly located in the arcuate nucleus of hypothalamus in which cells containing beta-endorphin after s.c. formalin injection also express pERK1/2, pCaMK-IIalpha and pIkappaB immunoreactivity. In addition, formalin-induced POMC mRNA expression was significantly reduced by 10 min, pretreatment with i.c.v. PD98059 (mitogen-activated protein kinase (MAPK) pathways inhibitor; 6.6 mug) and KN93 (pCaMK-II inhibitor; 20 mug). In conclusion, POMC mRNA expression in the arcuate nucleus of the hypothalamus was increased by inflammatory pain stimuli, in which pERK1/2, pCaMK-IIalpha and NFkappaB may play an important role in the expression of the hypothalamic POMC gene and beta-endorphin expression.

Topics: Analysis of Variance; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Calcium-Calmodulin-Dependent Protein Kinase Kinase; Formaldehyde; Gene Expression Regulation; I-kappa B Proteins; Male; Mice; Mice, Inbred ICR; Pain; Pro-Opiomelanocortin; RNA, Messenger; Time Factors

The present study was performed to characterize the differential molecular mechanisms of morphine and beta-endorphin which are injected intracerebroventiricularly in mice. In the immunoblot assay, the increases of phosphorylated extracellular signal-regulated protein kinase (pERK) as well as phosphorylated calcium/calmodulin-dependent protein kinase IIalpha (pCaMK-IIalpha) expression induced by noxious stimuli were attenuated by intracerebroventricular (i.c.v.) beta-endorphin pretreatment in the hypothalamus, but not by i.c.v. morphine pretreatment. In addition to these immunoblot results, immunohistochemical study also showed that the attenuation of pERK or pCaMK-IIalpha immunoreactivity elicited by i.c.v. pretreatment of beta-endorphin mainly occurred in the paraventricular nucleus of the hypothalamus (PVN). We also investigated the effect of morphine and beta-endorphin on pERK and pCaMK-IIalpha expression in the locus coeruleus (LC). I.c.v. injection of morphine significantly increased pERK as well as pCaMK-IIalpha expression in the locus coeruleus, while beta-endorphin increased only pCaMK-IIalpha in the LC. In addition, beta-endorphin significantly attenuated pERK expression induced by SP i.t. injection. These results suggest that the antinociceptive effects of supraspinally administered morphine and beta-endorphin are involved with differentially intracellular signal transduction molecules-pERK, pCaMK-IIalpha in the PVN and the LC.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Blotting, Western; Brain Chemistry; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Extracellular Signal-Regulated MAP Kinases; Formaldehyde; Immunohistochemistry; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Morphine; Pain; Paraventricular Hypothalamic Nucleus; Substance P

Even though inflammation is a traditional tool for the induction of hyperalgesia in many tissues, recent observations suggest that not all inflammatory processes produce this change. Tolerance to colorectal distension (CRD) is reduced in patients with acute ulcerative colitis but is increased in patients with chronic inflammatory bowel disease. This suggests that the nature of the inflammatory infiltrate influences visceral perception.. To test this hypothesis by assessing responses to CRD in mice with mild, acute or chronic colitis.. CRD responses were measured in mice with mild non-specific colitis, and dextran sodium sulphate (DSS)-induced acute and chronic colitis. Responses were compared with tissue infiltrate and damage, interleukin (IL)1beta and myeloperoxidase (MPO) activity and substance P, beta-endorphin and micro opioid receptor (MOR) expression.. Mild and acute colitis were associated with increased responsiveness to CRD. In contrast, CRD responses were not increased in mice with chronic colitis and this difference was not due to altered colonic wall compliance. MPO and IL1beta levels were greater in acute than in chronic colitis. Larger increases in tissue substance P were seen in acute than in chronic DSS, whereas CD4 T cells, beta-endorphin and MOR expression were evident only in chronic colitis. An inverse correlation was seen between substance P and MOR in these tissues.. Acute colitis increased responsiveness to CRD and is accompanied by an acute inflammatory infiltrate and increased tissue substance P. Chronic DSS is accompanied by an increase in beta-endorphin and MOR expression, and CD4 T cells, but no change in compliance or CRD responses. We conclude that acute inflammation generates hyperalgesia, whereas chronic inflammation involves infiltration by lymphocytes accompanied by MOR and beta-endorphin up regulation, and this provides an antinociceptive input that restores normal visceral perception.

Topics: Acute Disease; Animals; beta-Endorphin; CD4-Positive T-Lymphocytes; Chronic Disease; Colitis; Colon; Compliance; Interleukin-1beta; Male; Mice; Mice, Inbred BALB C; Neuropeptides; Pain; Pain Threshold; Physical Stimulation; Receptors, Opioid, mu; Substance P

Proopiomelanocortin (POMC)-derived beta-endorphin1-31 (END) released from immune cells inhibits inflammatory pain. We examined the expression of END and POMC mRNA encoding the signal sequence required for entry of the nascent polypeptide into the regulated secretory pathway in lymphocytes of rats with inflamed hindpaws. Within 12 h of inflammation, END increased in popliteal lymph nodes and at 96 h the intraplantar neutralization of END exacerbated pain. Lymphocytes expressed POMC, END, and full-length POMC mRNA. Semi-nested PCR revealed 8-fold increased exon 2-3 spanning POMC mRNA. Thus, painful inflammation enhances signal sequence-encoding lymphocytic POMC mRNA needed for regulated secretion of functionally active END.

Topics: Animals; beta-Endorphin; Flow Cytometry; Freund's Adjuvant; Gene Expression Regulation; Inflammation; Lymphocytes; Male; Pain; Pro-Opiomelanocortin; Protein Sorting Signals; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

Previous study has proven that microinjection of arginine vasopressin (AVP) into periaqueductal gray (PAG) raises the pain threshold, in which the antinociceptive effect of AVP can be reversed by PAG pretreatment with V2 rather than V1 or opiate receptor antagonist. The present work investigated the AVP effect on endogenous opiate peptides, oxytocin (OXT) and classical neurotransmitters in the rat PAG. The results showed that AVP elevated the concentrations of leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek) and beta-endorphin (beta-Ep), but did not change the concentrations of dynorphinA(1-13) (DynA(1-13)), OXT, classical neurotransmitters including achetylcholine (Ach), choline (Ch), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), dopamine (DA), norepinephrine (NE) and epinephrine (E), and their metabolic products in PAG perfusion liquid. Pain stimulation increased the concentrations of AVP, L-EK, M-Ek, beta-Ep, 5-HT and 5-HIAA (5-HT metabolic product), but did not influence the concentrations of DynA(1-13), OXT, the other classical neurotransmitters and their metabolic products. PAG pretreatment with naloxone - an opiate receptor antagonist completely attenuated the pain threshold increase induced by PAG administration of AVP, but local pretreatment of OXT or classical neurotransmitter receptor antagonist did not influence the pain threshold increase induced by PAG administration of AVP. The data suggested that AVP in PAG could induce the local release of enkephalin and endorphin rather than dynophin, OXT and classical neurotransmitters to participate in pain modulation.

Topics: Acetylcholine; Animals; Arginine Vasopressin; beta-Endorphin; Choline; Dopamine; Dose-Response Relationship, Drug; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Epinephrine; gamma-Aminobutyric Acid; Glutamic Acid; Male; Norepinephrine; Opioid Peptides; Oxytocin; Pain; Pain Threshold; Periaqueductal Gray; Rats; Rats, Sprague-Dawley; Serotonin

We have previously shown that microinjection of galanin into the arcuate nucleus of hypothalamus (ARC) produced antinociceptive effects in rats (Sun et al., 2003a). In this study, the neural pathway of galanin from ARC to midbrain periaqueductal gray (PAG) in nociceptive modulation was investigated. The hindpaw withdrawal latencies (HWLs) with noxious thermal and mechanical stimulation were assessed by the hotplate and the Randall Selitto tests. Intra-ARC administration of 0.1, 0.5, or 1 nmol of galanin induced significant increases in HWLs of rats. The galanin-induced increases in HWLs were inhibited by injection of 10 microg of the opioid receptor antagonist naloxone or 1 nmol of the mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) into PAG, suggesting that the antinociceptive effects induced by intra-ARC injection of galanin occur via the neural pathway from ARC to PAG. Furthermore, our results demonstrate that the galaninergic fibers directly innervated the beta-endorphinergic neurons in ARC by immunofluorescent methods. Taken together, our results suggest that galanin produces antinociceptive effects in the ARC of rats by activating the beta-endorphinergic pathway from ARC to PAG.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Fluorescent Antibody Technique; Galanin; Hindlimb; Hot Temperature; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Neural Pathways; Neurons; Pain; Periaqueductal Gray; Physical Stimulation; Rats; Rats, Wistar

Our previous study proved that hypothalamic paraventricular nucleus (PVH) plays an important role in acupuncture analgesia. The effect of acupuncture on the concentrations of arginine vasopressin (AVP), oxytocin (OXT), leucine-enkephaline (L-Ek), beta-endorphin (beta-Ep) and dynorphinA(1-13) (DynA(1-13)) was investigated in rat PVH. Electrical acupuncture of "Zusanli" points (St. 36) 30 min increased the AVP, not OXT, L-Ek, beta-Ep and DynA(1-13) concentrations in PVH tissue using micropunch and radioimmunoassay, which showed a negative relationship between the pain threshold and AVP concentrations in PVH tissue. Electrical acupuncture could elevate the AVP concentrations in PVH perfuse liquid during acupuncture, and then reduce the AVP concentrations in PVH perfuse liquid after acupuncture. But no change in OXT, L-Ek, beta-Ep and DynA(1-13) concentrations was detected in PVH perfuse liquid. Electrical acupuncture decreased the number of AVP, not OXT, L-Ek, beta-Ep and DynA(1-13) immunoreactive cells in PVH using immunocytochemistry. The results suggested that only AVP, not OXT and endogenous opiate peptides in PVH involved acupuncture analgesia in the rat.

Topics: Acupuncture Analgesia; Afferent Pathways; Animals; Arginine Vasopressin; beta-Endorphin; Dynorphins; Electric Stimulation; Enkephalin, Leucine; Extracellular Fluid; Hypothalamo-Hypophyseal System; Immunohistochemistry; Male; Neurons; Opioid Peptides; Oxytocin; Pain; Paraventricular Hypothalamic Nucleus; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Up-Regulation

The purpose of this report is to explore the mechanisms of hypercapnia-induced antinociception. We carried out three experiments, the first to confirm whether moderate hypercapnia induces anesthetic effects, the second to determine whether naloxone reverses the anesthetic effects, and the third to evaluate whether beta-endorphin is related to the anesthetic effects. In a pre-test, we determined the optimal CO(2) concentration in a chamber which would cause moderate hypercapnia in rats. Eighteen rats were divided into control, hypercapnia, and hypercapnia plus naloxone groups in experiment 1. The naloxone group rats were injected with naloxone (10 mg/kg) intraperitoneally before gas inhalation. After 60 min gas inhalation, 10% formalin was injected into the left rear paw of all rats, and nociceptive behaviors were observed for 1 h. In experiment 2, 11 rats were divided into control and hypercapnia groups. The brain was removed and fixed under pentobarbital anesthesia. Sections were immunostained for c-Fos and beta-endorphin (ACTH) with the ABC method. All neurons double-labeled for c-Fos and beta-endorphin (ACTH) in the arcuate nucleus were counted by blinded investigators. Moderate hypercapnia (PaCO(2) 83+/-7 mmHg) reduced nociceptive behavior in the formalin test and naloxone pre-treatment attenuated this phenomenon. However, beta-endorphin-producing neurons were not activated by CO(2) inhalation. Endogenous opioids are related to moderate, hypercapnia-induced anesthetic effects, but, beta-endorphin-producing neurons in the hypothalamus were not activated by the CO(2) inhalation stress.

Topics: Anesthetics, Inhalation; Animals; beta-Endorphin; Carbon Dioxide; Hypothalamus; Male; Naloxone; Narcotic Antagonists; Neurons; Pain; Pain Measurement; Pain Threshold; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Opioid

Electroacupuncture stimulation (EAS) is known to change brain neurotransmitter release. In the present study, we investigated the effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception. Rats were given "2/100 Hz" EAS, which stands for an asynchronous mode of stimulation, in which 2 Hz was alternated with 100 Hz, each lasting for 3 s, or "(2 + 100) Hz" EAS, a mode of stimulation in which 2 Hz stimulation was applied to the left hind leg simultaneously with 100 Hz stimulation on the right hind leg. The rats were subjected to the same total number of electrical stimulations in these two modes. Results were as follows: (1) 2/100 Hz EAS was 40% more potent than (2 + 100) Hz EAS (P < 0.01) in producing an anti-nociceptive effect. (2) Intrathecal (i.t.) injection of the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) blocked in a dose-dependent manner the anti-nociceptive effect produced by 2/100 Hz EAS but not by (2 + 100) Hz EAS, whereas i.t. injection of the kappa-opioid receptor antagonist norbinaltorphimide (Nor-BNI) blocked the anti-nociceptive effect induced by both modes of EAS. (3) I.t. injection of endomorphin-2 antiserum blocked in a dose-dependent manner the anti-nociceptive effect of 2/100 Hz EAS but not that of (2 + 100) Hz EAS, whereas i.t. injection of dynorphin antiserum blocked the anti-nociceptive effect induced by both modes of stimulation. (4) 2/100 Hz EAS increased the release of both endomorphin-2 and dynorphin, whereas (2 + 100) Hz EAS increased the release of dynorphin but not of endmorphin-2. We conclude that the more potent anti-nociceptive effect induced by 2/100 Hz EAS, as compared with that of (2 + 100) Hz EAS, was due, at least partly, to the synergistic interaction of endomorphin-2 and dynorphin in rat spinal cord.

Topics: Afferent Pathways; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Drug Synergism; Dynorphins; Electroacupuncture; Female; Narcotic Antagonists; Narcotics; Neurons, Afferent; Nociceptors; Pain; Pain Management; Pain Measurement; Rats; Rats, Wistar; Receptors, Opioid, kappa; Receptors, Opioid, mu; Reflex; Spinal Cord

This study aimed to investigate how local pain relief is mediated by laser therapy and how dose affects the relationship.. Inflammation was induced in the hind-paws of Wistar rats. Two groups of rats received 780-nm laser therapy (Spectra-Medics Pty Ltd.) at one of two doses (2.5 and 1 J/cm(2)). One group acted as a control. Scores of nociceptive threshold were recorded using paw pressure and paw thermal threshold measures.. A dose of 1 J/cm(2) had no statistically significant effect on antinociceptive responses. A dose of 2.5 J/cm(2) demonstrated a statistically significant effect on paw pressure threshold ( p < 0.029) compared to controls. There was no difference in paw thermal threshold responses and paw volumes at either dose. Immunohistochemistry in control animals demonstrated normal beta-endorphin containing lymphocytes in control inflamed paws but no beta-endorphin containing lymphocytes in rats that received laser at 2.5 J/cm(2).. The results confirm previous findings that the effect of laser therapy is dose-related. The mechanism of effect may occur via a differentiated pressure-sensitive neural pathway rather than a thermal-sensitive neural pathway. The significance of the immunohistochemistry findings remains unknown.

Topics: Animals; beta-Endorphin; Hindlimb; Inflammation; Low-Level Light Therapy; Lymphocytes; Male; Pain; Pain Threshold; Radiotherapy Dosage; Rats; Rats, Wistar

Topics: Animals; beta-Endorphin; Dronabinol; Humans; Keratinocytes; Mice; Pain; Rats; Receptor, Cannabinoid, CB2

To observe the analgesic effect of Zhitong Capsule (ZTC) and study its mechanism in adjuvant arthritis (AA) rats.. Forty-eight male Sprague-Dawley rats were randomly divided into six groups with 8 rats in each group. On the first day, except to those in the normal group that were treated with normal saline, the same amount of Freund's complete adjuvant (FCA) was given through intradermal injection into the right hind paw to all the rats in the other groups. From the 17th day of the modeling on, the rats in groups of ZTC were administered daily through gastrogavage with a dose of 1000, 500, 250 mg/kg respectively, while equal volume of normal saline was given to those in the normal group and model group, and an equal volume of aspirin (ASA) solution was given to rats in the ASA group through gastrogavage for 10 days, once per day, and on the 27th day, the analgesic effect of ZTC was measured with heat withdraw method. The activities and contents of superoxide dismutase (SOD) and lipid peroxides (LPO) in serum were observed by spectrophotometry, and the level of beta-endorphin (beta-EP) in hypothalamus were determined by the assay of immunohistochemistry.. ZTC showed significant effects on enhancing the pain threshold and at the same time it increased the activities of SOD and reduced the contents of LPO in serum. ZTC could also increase the level of beta-EP in hypothalamus.. ZTC has analgesic effect and its mechanism is probably related with its effect in inhibiting the level of oxygen free radicals in serum and increasing the level of beta-EP of hypothalamus in rats.

Topics: Analgesia; Animals; Arthritis, Experimental; beta-Endorphin; Hypothalamus; Lipid Peroxides; Male; Medicine, Chinese Traditional; Pain; Pain Threshold; Phytotherapy; Plant Preparations; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tissue Distribution

The opioid peptide beta-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.

Topics: Animals; beta-Endorphin; Carboxypeptidase H; Extremities; Immunohistochemistry; In Vitro Techniques; Inflammation; Leukocytes; Male; Microscopy, Immunoelectron; Norepinephrine; Pain; Pro-Opiomelanocortin; Proprotein Convertase 1; Proprotein Convertase 2; Rats; Rats, Wistar; Secretory Vesicles; Sympathomimetics

Stressful stimuli can activate the hypothalamo-pituitary-adrenal-axis and the endogenous opioid system. In addition, corticosterone and opioid release might cause analgesia. This rat study used adrenalectomy for corticosterone withdrawal and naloxone administration for opioid antagonism in order to study pain behavior and hypophyseal hormone release in the plasma after a formalin test. Twelve days before the formalin testing, male Sprague Dawley rats underwent adrenalectomy or sham-adrenalectomy, and non-operated rats were used as reference. The number of flinches and the duration of licking or biting behavior were measured during the early and late phase. In reference and sham-operated rats, injection of formalin 5% resulted in a marked pain behavior in the early and late phase with significant increases in ACTH and corticosterone plasma levels. In adrenalectomized rats, pain behavior was decreased during both phases. Naloxone, administered before the late phase, did not alter pain behavior in sham or reference rats, whereas in adrenalectomized rats pain reactivity returned to those levels observed in reference rats. Beta-endorphin plasma levels above the detection limit were more frequently found in adrenalectomized rats. Thyrotropin and prolactin levels were not different between studied groups. We speculate that the observed reduced pain behavior in adrenalectomized rats after formalin, is the result of an increased production of pro-opiomelanocortin, the pro-drug of both adrenocorticotrophic hormone and beta-endorphin.

Topics: Adrenalectomy; Animals; Behavior, Animal; beta-Endorphin; Corticosterone; Formaldehyde; Injections, Intraperitoneal; Male; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pituitary Hormones; Prolactin; Rats; Rats, Sprague-Dawley; Thyrotropin

Intrathecal (i.t.) pretreatment with a low dose (0.3 nmol) of morphine causes an attenuation of i.t. morphine-produced analgesia; the phenomenon has been defined as morphine-induced antianalgesia. The opioid-produced analgesia was measured with the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with low dose (0.3 nmol) of morphine time dependently attenuated i.t. morphine-produced (3.0 nmol) TF inhibition and reached a maximal effect at 45 min. Intrathecal pretreatment with morphine (0.009-0.3 nmol) for 45 min also dose dependently attenuated morphine-produced TF inhibition. The i.t. morphine-induced antianalgesia was dose dependently blocked by the nonselective mu-opioid receptor antagonist (-)-naloxone and by its nonopioid enantiomer (+)-naloxone, but not by endomorphin-2-sensitive mu-opioid receptor antagonist 3-methoxynaltrexone. Blockade of delta-opioid receptors, kappa-opioid receptors, and N-methyl-D-aspartate (NMDA) receptors by i.t. pretreatment with naltrindole, nor-binaltorphimine, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), respectively, did not affect the i.t. morphine-induced antianalgesia. Intrathecal pretreatment with antiserum against dynorphin A(1-17), [Leu]-enkephalin, [Met]-enkephalin, beta-endorphin, cholecystokinin, or substance P also did not affect the i.t. morphine-induced antianalgesia. The i.t. morphine pretreatment also attenuated the TF inhibition produced by opioid muagonist [D-Ala2, N-Me-Phe4,Gly-ol5]-enkephalin, delta-agonist deltorphin II, and kappa-agonist U50,488H. It is concluded that low doses (0.009-0.3 nmol) of morphine given i.t. activate an antianalgesic system to attenuate opioid mu-, delta-, and kappa-agonist-produced analgesia. The morphine-induced antianalgesia is not mediated by the stimulation of opioid mu-, delta-, or kappa-receptors or NMDA receptors. Neuropeptides such as dynorphin A(1-17), [Leu]-enkephalin, [Met]-enkephalin, beta-endorphin, cholecystokinin, and substance P are not involved in this low-dose morphine-induced antianalgesia.

Topics: Analgesia; Animals; beta-Endorphin; Dizocilpine Maleate; Drug Interactions; Drug Tolerance; Dynorphins; Enkephalins; Male; Mice; Morphine; Naloxone; Naltrexone; Oligopeptides; Pain; Pain Measurement; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Spinal Cord; Substance P

The aim of the present study was to determine the effects of distinct categories of stressors on beta-endorphin (beta-EP) release in the arcuate nucleus (ArcN) and nucleus accumbens (NAcb) using in vivo microdialysis. Adult male rats were implanted with a cannula aimed at either the NAcb or the ArcN. On the day of testing, a 2 mm microdialysis probe was inserted into the cannula, and artificial cerebrospinal fluid was infused at 2.0 microl/min. After three baseline collections, animals either had a clothespin applied to the base of their tail for 20 min (a physical/tactile stressor), were exposed to fox urine odour for 20 min (a psychological stressor/species-specific threat), or were administered 2.4 g ethanol/kg body weight, 16.5% w/v, i.p. (a chemical/pharmacological stressor) with control animals receiving an equivalent volume of saline. Both tail-pinch and fox odour significantly increased beta-EP release from the ArcN (P<0.05), whilst only tail-pinch enhanced beta-EP release from the NAcb (P<0.01). On the other hand, alcohol stimulated beta-EP release in the NAcb as compared with saline-treated controls (P<0.01), but not in the ArcN. Although the increase in extracellular beta-EP produced by the other stressors was relatively rapid, there was a 90-min delay before alcohol administration caused beta-EP levels to exceed that of saline-injected controls. In conclusion, the fact that physical and fear-inducing psychological stressors stimulate beta-EP release in the ArcN and only physical stressors stimulate beta-EP release in the NAcb, indicates that stressors with different properties are processed differently in the brain. Also, an injection of alcohol caused a delayed increase of beta-EP in the NAcb but not the ArcN, indicating that alcohol may recruit a mechanism that is, at least partially, distinct from stress-related pathways.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Central Nervous System Depressants; Ethanol; Male; Microdialysis; Nucleus Accumbens; Odorants; Pain; Rats; Rats, Sprague-Dawley; Stress, Physiological; Tail

Corticotropin-releasing hormone (CRH) mainly regulates the synthesis and secretion of adrenocorticotropin (ACTH) in the anterior pituitary (AP). By using CRH-deficient mice (CRH KO), we investigated the role of CRH in the processing of proopiomelanocortin (POMC), a precursor of ACTH, beta-lipotropic hormone, and beta-endorphin (EP). In the basal condition, the plasma ACTH level was similar in CRH KO and wild-type mice (WT), while its response to pain stress in CRH KO was smaller than that in WT. Immunoreactive (ir) beta-EP contents in the AP of CRH KO were not significantly different from those of WT. In order to determine the different molecule profile of POMC-related peptides between WT and CRH KO, ir beta-EP contents extracted from AP of WT and CRH KO were assayed by gel filtration chromatography. The gel filtration analyses revealed that a higher molecular weight form of ir beta-EP, putative POMC, was increased in CRH KO, but the beta-EP peak level was small and similar between two groups. These results suggest that CRH has little influence on the basal release of ACTH and prohormone convertase-2 processing enzyme. On the other hand, it is essential for ACTH secretion under stress conditions, and CRH would affect on the prohormone convertase-1/3 processing enzyme in AP.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; Animals; beta-Endorphin; beta-Lipotropin; Chromatography, Gel; Corticotropin-Releasing Hormone; Hypophysectomy; Mice; Mice, Inbred C57BL; Mice, Knockout; Pain; Pituitary Gland, Anterior; Pro-Opiomelanocortin; Radioimmunoassay

Antagonistic properties of buprenorphine for epsilon- and micro -opioid receptors were characterized in beta-endorphin- and [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO)-induced antinociception, respectively, with the tail-flick test in male ICR mice. epsilon-Opioid receptor agonist beta-endorphin (0.1-1 micro g), micro -opioid receptor agonist DAMGO (0.5-20 ng), or buprenorphine (0.1-20 micro g) administered i.c.v. dose dependently produced antinociception. The antinociception induced by 10 micro g of buprenorphine given i.c.v. was completely blocked by the pretreatment with beta-funaltrexamine (beta-FNA) (0.3 micro g i.c.v.), indicating that the buprenophine-induced antinociception is mediated by the stimulation of the micro -opioid receptor. The antinociceptive effects induced by beta-endorphin (1 micro g i.c.v.) and DAMGO (16 ng i.c.v.) were dose dependently blocked by pretreatment with smaller doses of buprenorphine (0.001-1 micro g i.c.v.), but not by a higher dose of buprenorphine (10 micro g i.c.v.). beta-FNA at a dose (0.3 micro g i.c.v.) that strongly attenuated DAMGO-induced antinociception had no effect on the antinociception produced by beta-endorphin (1 micro g i.c.v.). However, pretreatment with buprenorphine (0.1-10 micro g) in mice pretreated with this same dose of beta-FNA was effective in blocking beta-endorphin-induced antinociception. beta-FNA was 226-fold more effective at antagonizing the antinociception induced by DAMGO (16 ng i.c.v.) than by beta-endorphin (1 micro g i.c.v.). The antinociception induced by delta-opioid receptor agonist [d-Ala2]deltorphin II (10 micro g i.c.v.) or kappa1-opioid receptor agonist trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamine methanesulfonate salt [(-)-U50,488H] (75 micro g i.c.v.) was not affected by pretreatment with buprenorphine (0.1-1.0 micro g i.c.v.). It is concluded that buprenorphine, at small doses, blocks epsilon-opioid receptor-mediated beta-endorphin-induced antinociception and micro -opioid receptor-mediated DAMGO-induced antinociception, and at high doses produces a micro -opioid receptor-mediated antinociception.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; beta-Endorphin; Buprenorphine; Disease Models, Animal; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Naltrexone; Narcotic Antagonists; Oligopeptides; Pain; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Time Factors

Endothelin-1 (ET-1) is a newly described pain mediator that is involved in the pathogenesis of pain states ranging from trauma to cancer. ET-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. While it is able to trigger pain through its actions on endothelin-A (ET(A)) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ET(B)) receptors. Here we map a new endogenous analgesic circuit, in which ET(B) receptor activation induces the release of beta-endorphin from keratinocytes and the activation of G-protein-coupled inwardly rectifying potassium channels (GIRKs, also named Kir-3) linked to opioid receptors on nociceptors. These results indicate the existence of an intrinsic feedback mechanism to control peripheral pain in skin, and establish keratinocytes as an ET(B) receptor-operated opioid pool.

Topics: Analgesia; Animals; beta-Endorphin; Cells, Cultured; Endothelin-1; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; Keratinocytes; Male; Pain; Pain Measurement; Potassium Channels; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Receptor, Endothelin B; Receptors, Endothelin; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Signal Transduction; Skin

Opioids remain the most efficacious pharmacological agents for various clinical pain syndromes. Recently, various engineered cells capable of secreting opioidergic peptides have been applied to relieve pain in animal models. In vivo gene delivery by viruses encoding endogenous opioids has also been used with success. In this study, we attempted non-viral intrathecal in vivo gene delivery by electroporation to induce analgesia. Thirty Sprague-Dawley rats were used in this study, six in each of five groups. Rats were treated as follows: vehicle without electroporation (group A), vehicle with electroporation (group B), 100 microg of pCMV-hPOMC plasmid without electroporation (group C), or 100 microg of pCMV-hPOMC plasmid with electroporation (group D). Group E was treated with both pCMV-hPOMC plasmid and electroporation, and given naloxone (1mg/kg) 1h before the formalin test. The tail flick, paw withdrawal latency from radiant heat, and formalin test results for each groups were compared. Radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the levels of expression of beta-endorphin in the spinal cord. beta-Endorphin expression was localized by immunohistochemistry. A significant decrease in the number of flinches in phase 2 of the formalin test was observed in the group treated with both plasmid and electroporation (group D), whereas the other measures of pain did not differ between groups. RIA and RT-PCR both showed increased expression of beta-endorphin in group D. The expression of beta-endorphin was highest in laminae I and II of the dorsal horn of the spinal cord. We conclude that electroporation successfully delivered intrathecally administered pCMV-hPOMC into the dorsal horn cells of the spinal cord, and induced analgesia in phase 2 of the formalin test in rats.

Topics: Analgesia; Animals; beta-Endorphin; Disease Models, Animal; DNA, Complementary; Drug Delivery Systems; Electroporation; Humans; Male; Pain; Pain Measurement; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Spinal Cord

Clients report more pain at some times of day than at others due, in part, to the temporal variation of the body's inhibitory pain response. The analgesic effectiveness of morphine varies with the time of day, perhaps due to the inhibiting or enhancing effects of the drug on plasma beta-endorphin (BE). This experiment was designed to examine the timed effects of morphine on the pain-induced BE response. Six groups of treatment mice (injected with morphine sulfate) and 6 groups of control mice (injected with saline) were exposed to an acute pain stimulus at 4-h intervals, and blood was collected. Plasma BE was analyzed using radioimmunoassay. Control mice showed a robust circadian BE-response rhythm with a peak at 0000 and a nadir at 1200, whereas the BE response of mice that received morphine was arrhythmic. Animals that received morphine tolerated the noxious stimulus longer, but the analgesia varied with time of day. These results indicate that morphine abolishes the rhythmic BE response to pain and does not inhibit pain equally at all times of day. Morphine doses should be titrated to maximize the endogenous pain control system while achieving analgesia with decreased dosages.

Topics: Acute Disease; Analgesics, Opioid; Animals; Behavior, Animal; beta-Endorphin; Chronobiology Disorders; Chronotherapy; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Monitoring; Humans; Male; Mice; Mice, Inbred DBA; Morphine; Pain; Pain Measurement; Pain Threshold; Radioimmunoassay; Reaction Time; Time Factors; Treatment Outcome

Sucrose is an effective analgesic for procedural pain in preterm infants. It has been hypothesized that its analgesic effects are mediated by the release of endogenous opioid neurotransmitters such as beta-endorphin.. To determine whether intraoral administration of sucrose was associated with an increase in serum beta-endorphin concentrations in preterm infants with a gestation period less than 29 weeks who were not exposed to a painful stimulus.. We performed a prospective open-label study in preterm infants admitted to 2 tertiary neonatal intensive care units. Each infant received a single dose of 30% sucrose intraorally during a 1- to 2-minute period. A blood sample was obtained using an indwelling arterial catheter to determine beta-endorphin concentration immediately before and 2 to 5 minutes after the commencement of sucrose administration.. We enrolled 11 preterm infants with a mean +/- SD gestational age of 27.2 +/- 0.9 weeks and a mean +/- SD birth weight of 1018 +/- 238 g (1.02 +/- 0.24 kg) at a mean +/- SD postnatal age of 3.0 +/- 2.5 days. The mean +/- SD beta-endorphin concentration before and after sucrose administration was 60.4 +/- 30.5 pg/mL and 57.4 +/- 22.4 pg/mL, respectively (P =.45). No adverse events were observed during the study procedures.. Intraoral administration of sucrose in preterm infants did not lead to an increase in serum beta-endorphin concentrations at a point in time when the analgesic effects of sucrose were presumed to be present.

Topics: Administration, Oral; beta-Endorphin; Critical Care; Female; Humans; Infant, Newborn; Infant, Premature; Male; Pain; Pain Measurement; Prospective Studies; Sucrose

In painful inflammation, exogenous as well as endogenous corticotropin-releasing hormone (CRH) can release opioid peptides (mainly beta-endorphin) from various types of immune cells and produce antinociception by activating opioid receptors on peripheral sensory nerve endings. CRH mediates its central effects through two high-affinity membrane receptors, the CRH receptor subtypes 1 and 2. It is unclear at present whether the peripheral antinociceptive effects of CRH are mediated through CRH receptor 1 (CRH R1) or CRH receptor 2 (CRH R2). Employing a double-immunocytochemical technique, this study investigated in Wistar rats with Freund's complete adjuvant-induced hind paw inflammation whether immune cells within blood and inflamed subcutaneous tissue express CRH R1 and/or CRH R2 together with the opioid peptide beta-endorphin (END). Additionally, we examined using selective CRH R1 and CRH R2 antagonists whether peripheral CRH-induced antinociception is mediated by the respective CRH receptor subtypes. We found a high degree of co-expression of END together with both CRH R1 and CRH R2 in macrophage/monocytes, granulocytes and lymphocytes within blood and inflamed subcutaneous tissue. Also we observed a high degree of co-localization of CRH R1 and CRH R2 receptors on circulating and resident immune cells. Both the selective CRH R1 antagonist CP-154,526 and the selective CRH R2 antagonist astressin 2B significantly attenuated peripheral antinociceptive effects of CRH indicating the involvement of both CRH receptor subtypes. Taken together, these findings suggest that in inflammatory pain CRH-induced peripheral antinociception is mediated via both CRH R1 and CRH R2 located on END containing immune cells within inflamed sites.

Topics: Animals; beta-Endorphin; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Freund's Adjuvant; Inflammation; Male; Opioid Peptides; Pain; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone

The literature indicates that beta-endorphin can be found in the mononuclear cells of peripheral blood. In the present experiments the endorphin content of granulocytes was studied, compared to lymphocytes as reference cells. Granulocytes as well, as lymphocytes contain endorphin. The granulocytes' endorphin content is much higher. Both lymphocytes and granulocytes are also able to take up endorphin from the milieu.

Topics: Animals; beta-Endorphin; Cell Count; Flow Cytometry; Fluorescent Antibody Technique; Granulocytes; Inflammation; Lymphocytes; Male; Pain; Rats; Rats, Wistar

Self-injurious behavior (SIB) is an untreatable and often life-threatening problem among individuals with developmental disorders, especially those diagnosed with autism. Functioning, relationships and processing of the proopiomelanocortin (POMC) system are "uncoupled" in subgroups of self-injuring individuals resulting in different ratios of ACTH and opioids in the bloodstream, particularly under conditions of stress. In this study, relations between SIB and POMC were evaluated in a multi-year study of the largest prospective sample studied to date. Observations were collected on palmtop computers for 45 treatment-resistant patients who exhibited chronic SIB. Behavior of each subject was observed in natural settings without disruption or intrusion, for continuous, 2.5-h periods, two times a day (morning and afternoon), 4 days a week for two consecutive weeks, for a total of 40 h/subject. Blood was collected in the morning, late afternoon and immediately after an SIB episode on two separate occasions separated by at least 6 months. Levels of beta-endorphin (beta E) and ACTH were assayed by RIA. We discovered that the SIB was the best predictor of subsequent SIB. Moreover, the majority of subjects exhibited this contagious pattern of SIB. Levels of POMC fragments were reliable over a 6- to 9-month period. Subjects exhibiting POMC disregulation characterized by high morning levels of beta E had the highest transitional probabilities of SIB (i.e. contagious patterns; F=8.17, P<0.01). These findings suggest that subjects with "contagious" SIB may represent a behavioral phenotype associated with disregulated expression of the POMC gene.

Topics: Adrenocorticotropic Hormone; Autistic Disorder; beta-Endorphin; Disease Progression; Humans; Pain; Pro-Opiomelanocortin; Probability; Prospective Studies; Self-Injurious Behavior

To investigate the effect of essential oil of Radix Aangelicae Dahuricae (EOAD) on beta-endorphin Adrenocorticotropic hormone(ACTH), Nitric oxide (NO) and Proopiomelanocortin (POMC) of pain model rats induced by formaldehyde.. beta-endorphin and ACTH were detected with radio-immunity, the amount of masculine cell expression of Proopiomelanocortin mRNA in hypothalamus, and brainstem of pain model was detected with in situ hybridization and NO with chemical method.. EOAD could increase beta-endorphin, NO and the amount of masculine cell expression of Proopiomelanocortin mRNA significantly in hypothalamus and brainstem of rats.. EOAD which may be central analgesic, is associated with endogenous opiate-like substance such as POMC and beta-endorphin.

Topics: Adrenocorticotropic Hormone; Analgesics; Angelica; Animals; beta-Endorphin; Drugs, Chinese Herbal; Female; Formaldehyde; Hypothalamus; Male; Nitric Oxide; Oils, Volatile; Pain; Plant Roots; Plants, Medicinal; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; RNA, Messenger

Pain can be effectively controlled by endogenous mechanisms based on neuroimmune interactions. In inflamed tissue immune cell-derived opioid peptides activate opioid receptors on peripheral sensory nerves leading to potent analgesia. This is brought about by a release of opioids from inflammatory cells after stimulation by stress or corticotropin-releasing hormone (CRH). Immunocytes migrate from the circulation to inflamed tissue in multiple steps, including their rolling, adhesion, and transmigration through the vessel wall. This is orchestrated by adhesion molecules on leukocytes and vascular endothelium. Intercellular adhesion molecule-1 [ICAM-1 (or CD54)] is expressed by endothelium and mediates adhesion and extravasation of leukocytes. The goal of this study was to show that ICAM-1 regulates the homing of opioid-producing cells and the subsequent generation of analgesia within sites of painful inflammation. This was accomplished using immunofluorescence, flow cytometry, and behavioral (paw pressure) testing. We found that ICAM-1 is upregulated on the vascular endothelium, simultaneously with an enhanced immigration of opioid-containing immune cells into inflamed paw tissue. The intravenous administration of a monoclonal antibody against ICAM-1 markedly decreased the migration of opioid-containing leukocytes and of granulocytes, monocytes-macrophages, and T cells to the inflamed tissue. At the same time, circulating immunocytes increased in numbers, and macroscopic inflammation (hyperalgesia, paw volume, and paw temperature) remained primarily unchanged. Most importantly, peripheral opioid analgesia elicited either by cold water swim stress or by intraplantar administration of CRH was dramatically reduced. Together, these findings indicate that ICAM-1 expressed on vascular endothelium recruits immunocytes containing opioids to promote the local control of inflammatory pain.

Topics: Analgesia; Animals; Antibodies; beta-Endorphin; Cell Adhesion; Cell Movement; Forelimb; Inflammation; Intercellular Adhesion Molecule-1; Leukocytes; Male; Models, Immunological; Neuroimmunomodulation; Pain; Rats; Rats, Wistar; Up-Regulation

This paper reports that regulators of G-protein signalling (RGS) proteins modulate the timing and amplitude of opioid signals by a push-pull mechanism. This is achieved without noticeable changes in the binding properties of opioids, e.g. beta-endorphin to mu-opioid receptors. The expression of RGS proteins was reduced by blocking their mRNA with antisense oligodeoxynucleotides (ODN). Knock down of RGS2 or RGS3 diminished morphine and beta-endorphin analgesia, whereas that of RGS9 or RGS12 enhanced this activity. In mice with impaired RGS9, but not impaired RGS2, the potency and, in particular, the duration of opioid antinociception increased. Further, the animals did not exhibit acute tolerance generated by a single and efficacious dose of morphine, nor did they develop tolerance after a daily i.c.v. injection of the opioid for 4 days. In a model of sustained morphine treatment, the impairment of RGS9 proteins facilitated increases in the response to the delivered opioid. This was only effective for 2--3 h after the subcutaneous implantation of an oily morphine pellet; later, tolerance developed. To reduce the impact of the chronic morphine acting on opioid receptors, other RGS proteins presumably substitute the GTPase-activating function of RGS9 on morphine-activated G-alpha-GTP subunits. The desensitization of mu-opioid receptors appears to be a cell membrane-limited process facilitated by RGS9's sequestering of agonist-segregated G alpha subunits.

Topics: Analgesia; Analgesics, Opioid; Animals; beta-Endorphin; Brain Chemistry; Drug Implants; Gene Targeting; GTP Phosphohydrolases; GTP-Binding Proteins; GTPase-Activating Proteins; Guanosine Triphosphate; Heterotrimeric GTP-Binding Proteins; Humans; Injections, Intraventricular; Macromolecular Substances; Male; Mice; Models, Neurological; Morphine; Nerve Tissue Proteins; Oligodeoxyribonucleotides, Antisense; Pain; Protein Binding; Receptors, Opioid, mu; Reverse Transcriptase Polymerase Chain Reaction; RGS Proteins; RNA, Messenger; Signal Transduction; Tachyphylaxis

The roles of endogenous opioid peptides in the brain in the modulation of nocifensive responses to formalin in ICR mice were studied. Mice were pretreated intracerebroventricularly (i.c.v.) with rabbit antiserum against beta-endorphin, [Leu5]enkephalin, [Met5]enkephalin or dynorphin A-(1-17) 1 h prior to intraplantar injection of formalin (0.5%, 25 microl) and the nocifensive licking responses were then observed. Pretreatment of mice with antiserum against beta-endorphin enhanced the second phase, but not the first phase of the nocifensive responses to formalin. Pretreatment with antiserum against [Leu5]enkephalin also caused a small but statistically significant enhancement of the second phase, but not the first phase of nocifensive responses to formalin. On the other hand, pretreatment with antiserum against [Met5]enkephalin or dynorphin A-(1-17) did not affect the nocifensive response to formalin. Our results indicate that beta-endorphinergic, and to a lesser extent, [Leu5]enkephalinergic systems are activated at the supraspinal sites to attenuate the nocifensive responses to formalin stimulation.

Topics: Animals; beta-Endorphin; Dynorphins; Enkephalin, Leucine; Enkephalin, Methionine; Formaldehyde; Immune Sera; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Nociceptors; Opioid Peptides; Pain

Inflammatory pain can be effectively controlled by an interaction of opioid receptors on peripheral sensory nerve terminals with opioid peptides released from immune cells upon stressful stimulation. To define the source of opioid peptide production, we sought to identify and quantify populations of opioid-containing cells during the course of Freund's complete adjuvant-induced hind paw inflammation in the rat. In parallel, we examined the development of stress-induced local analgesia in the paw.. At 2, 6, and 96 h after Freund's complete adjuvant inoculation, cells were characterized by flow cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against cell surface antigens and by immunohistochemistry using a polyclonal antibody to beta-endorphin. After magnetic cell sorting, the beta-endorphin content was quantified by radioimmunoassay. Pain responses before and after cold water swim stress were evaluated by paw pressure thresholds.. In early inflammation, 66% of opioid peptide-producing (3E7+) leukocytes were HIS48+ granulocytes. In contrast, at later stages (96 h), the majority of 3E7+ immune cells were ED1+ monocytes or macrophages (73%). During the 4 days after Freund's complete adjuvant inoculation, the number of 3E7+ cells increased 5.6-fold (P < 0.001, Kruskal-Wallis test) and the beta-endorphin content in the paw multiplied 3.9-fold (P < 0.05, Kruskal-Wallis test). In parallel, cold water swim stress-induced analgesia increased by 160% (P < 0.01, analysis of variance).. The degree of endogenous pain inhibition is proportional to the number of opioid peptide-producing cells, and distinct leukocyte lineages contribute to this function at different stages of inflammation. These mechanisms may be important for understanding pain in immunosuppressed states such as cancer, diabetes, or AIDS and for the design of novel therapeutic strategies in inflammatory diseases.

Topics: Analgesia; Animals; Antibodies, Monoclonal; beta-Endorphin; Fluorescent Dyes; Hematopoietic Stem Cells; Immunohistochemistry; Immunomagnetic Separation; Inflammation; Leukocyte Common Antigens; Leukocytes; Lymphocytes; Male; Opioid Peptides; Pain; Pain Measurement; Radioimmunoassay; Rats; Rats, Wistar

The source and regulatory mechanisms that elevate beta-endorphin (beta-EP) approximately twofold higher than circulating plasma levels in the colostrum of lactating mothers are still unknown, and no studies have examined beta-EP availability previously during maturation phases of human milk. Therefore, the aim of this study was to determine whether concentrations of beta-EP vary over time between colostrum, transitional, and mature breast-milk and to evaluate whether this depends on the method of delivery.. Mothers of healthy full-term and pre-term newborn infants who planned to breast-feed their newborn infants were considered for this study. They were consecutively recruited in one of 3 groups of 14, according to delivery method: group 1, vaginal delivery at term (gestational age 40.2 +/- 0.3 weeks; birth weight, 3.48 +/- 0.09 kg); group 2, preterm vaginal delivery (gestational age, 35.6 +/- 0.3 weeks; birth weight, 2.49 +/- 0.08 kg); and group 3, at-term elective cesarean section (gestational age, 39.0 +/- 0.3 weeks; birth weight, 3.32 +/- 0.14 kg). Three consecutive breast milk samples were obtained on the fourth day after birth, before each mother's discharge, and thereafter on the 10th and 30th postpartum days, close to expression of the colostrum, transitional, and mature milk production phases, respectively, to test beta-EP concentrations (beta-Endorphin 125I RIA; INCSTAR Corporation, Stillwater, MN). Data are presented as mean +/- standard deviation. Statistical comparison of beta-EP concentration among the three lactating mother groups was performed using the Kruskal-Wallis nonparametric test. In addition, to test the hypothesis of a trend toward smaller values with time of beta-EP, the authors computed within each mother group a P value per trend (Kruskal-Wallis test) of beta-EP concentration averages on the 4th, 10th, and 30th days, respectively. Student's t test for independent samples was used for the analysis of the other data. The 0.05 significance level was used in the statistical analysis. All computations were made by computer.. Colostrum beta-EP concentrations on the fourth postpartum day of group 1 and group 2 mothers who were delivered of a neonate vaginally, at term, or prematurely were significantly higher (P < 0.01) than colostrum levels of group 3 mothers who underwent cesarean section. Group 2 mothers who were delivered of a neonate vaginally and prematurely presented the highest beta-EP concentrations (P < 0.05), lasting until the transitional milk phase (10th day). No significant differences were found across all 3 groups of lactating mothers in mature milk (30th day) beta-EP concentrations. In addition, the beta-EP trend toward smaller values with time within each of the three groups on days 4, 10, and 30 was statistically significant (P < 0.01 per trend).. It is hypothesized that elevated beta-EP concentrations in colostrum and transitional milk of mothers who were vaginally delivered of infants may contribute to postnatal fetal adaptation, to overcoming birth stress of natural labor and delivery, and at the same time to the postnatal development of several related biologic functions of breast-fed infants.

Topics: Adult; beta-Endorphin; Cesarean Section; Colostrum; Female; Humans; Infant, Newborn; Infant, Premature; Labor, Obstetric; Lactation; Longitudinal Studies; Milk, Human; Pain; Pregnancy

Male rats exhibit significantly greater antinociception following central administration of morphine than female rats. The present study examined potential differences in beta-endorphin (5.2-26 microg) antinociception elicited from the ventrolateral periaqueductal gray in adult sham-operated and gonadectomized male and female rats. Male rats displayed significantly greater peak (30 min) tail-flick latencies across the entire range of beta-endorphin doses administered into the ventrolateral periaqueductal gray than female rats tested during the estrous phase of the estrous cycle. Adult gonadectomy failed to appreciably change the pattern of this effect in either males of females. Thus, antinociception elicited from the ventrolateral periaqueductal gray by beta-endorphin, like morphine, is sensitive to sex differences.

Topics: Analysis of Variance; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Female; Male; Microinjections; Nociceptors; Orchiectomy; Ovariectomy; Pain; Pain Measurement; Periaqueductal Gray; Rats; Rats, Sprague-Dawley; Sex Factors

The effect of (+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5, 10-imine maleate (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) injected intrathecally (i.t.) on the inhibition of the tail-flick response induced by morphine, D-Ala(2)-NmePhe(4)-Gly-ol-enkephalin (DAMGO), beta-endorphin, D-Pen(2,5)-enkephalin (DPDPE), or ¿(trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide)¿ (U50, 488H) administered i.t. was studied in ICR mice. The i.t. injection of MK-801 (2 microg) or CNQX (1 microg) alone did not affect the basal tail-flick response. Morphine (0.2 microg), DAMGO (0.8 ng), beta-endorphin (0.1 microg), DPDPE (0.5 microg) or U50, 488H (6 microg) caused only slight inhibition of the tail-flick response. CNQX injected i.t., but not MK-801, enhanced the inhibition of the tail-flick response induced by i.t. administered morphine, DAMGO, DPDPE or U50, 488H. However, CNQX or MK-801 injected i.t. was not effective in enhancing the inhibition of the tail-flick response induced by beta-endorphin administered i.t. The potentiating effect of CNQX on tail-flick inhibition induced by morphine, DAMGO, DPDPE or U50, 488H was blocked by naloxone (from 1 to 20 microg), yohimbine (from 1 to 20 microg) or methysergide (from 1 to 20 microg) injected i.t. in a dose-dependent manner. Our results suggest that the blockade of AMPA/kainate receptors located in the spinal cord appears to be involved in enhancing the inhibition of the tail-flick response induced by stimulation of spinal mu-, delta-, and kappa-opioid receptors. Furthermore, this potentiating action may be mediated by spinal noradrenergic and serotonergic receptors. However, N-methyl-D-aspartate receptors may not be involved in modulating the inhibition of the tail-flick response induced by various opioids administered spinally.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; 6-Cyano-7-nitroquinoxaline-2,3-dione; Analgesics, Opioid; Animals; beta-Endorphin; Dizocilpine Maleate; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Excitatory Amino Acid Antagonists; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Pain; Spinal Cord; Time Factors

Opioid-containing immunocytes migrate to inflamed sites where they release beta-endorphin which activates peripheral opioid receptors and produces analgesia. The immigration of immunocytes to sites of inflammation is mediated by adhesion molecules. In this study, the expression of L-, P-, E-selectin and platelet-endothelial adhesion molecule-1 (PECAM-1) in relation to beta-endorphin expression was analyzed by immunohistochemistry in inflamed tissues. The proportion of immunocytes expressing L-selectin was increased in inflamed lymph nodes and subcutaneous paw tissue. P-selectin and PECAM-1 were constitutively expressed on endothelia of noninflamed lymph nodes and subcutaneous tissue and were upregulated in inflammation. beta-endorphin positive cells expressed L-selectin in lymph nodes and subcutaneous tissue. Upregulation of P-selectin and PECAM-1 and the co-localization of L-selectin and beta-endorphin in immunocytes suggest an important role of these adhesion molecules for the recruitment of immunocytes containing beta-endorphin to sites of painful inflammation.

Topics: Animals; beta-Endorphin; Cell Adhesion Molecules; Chemotaxis, Leukocyte; Disease Models, Animal; E-Selectin; Freund's Adjuvant; Hindlimb; Immunohistochemistry; Inflammation; L-Selectin; Lymph Nodes; Male; P-Selectin; Pain; Platelet Endothelial Cell Adhesion Molecule-1; Rats; Rats, Wistar; Skin; Up-Regulation

The effect of antiserum against [Met(5)]-enkephalin, [Leu(5)]-enkephalin, beta-endorphin, or dynorphin A-(1-13) administered intracerebroventricularly (i.c.v.) or intrathecally (i. t.) on immobilization-induced antinociception was studied in ICR mice. Antinociception was assessed by the tail-flick assay. Immobilization of the mouse increased inhibition of the tail-flick response at least 1 h. The i.c.v. or i.t. injection with antiserum against dynorphin A-(1-13) at the dose of 200 microg significantly attenuated immobilization-induced inhibition of the tail-flick response. However, antiserum against [Met(5)]-enkephalin, [Leu(5)]-enkephalin, or beta-endorphin did not affect the immobilization stress-induced antinociception. Furthermore, i.c.v. or i.t. injection with nor-binaltorphimine (Nor-BNI; from 1 to 20 microg) effectively inhibited immobilization stress-induced inhibition of the tail-flick response in a dose-dependent manner. However, beta-FNA (from 0.5 to 2 microg) or naltrindole (from 1 to 20 microg) administered i.c.v. or i.t. did not affect immobilization stress-induced antinociception. Our results suggest that supraspinally and spinally located dynorphin appears to be involved in the production of immobilization stress-induced antinociception via stimulating kappa-opioid receptors.

Topics: Animals; beta-Endorphin; Cerebral Ventricles; Dynorphins; Enkephalin, Leucine; Enkephalin, Methionine; Immune Sera; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Pain; Pain Measurement; Reaction Time; Restraint, Physical; Stress, Psychological

While transplants of adrenal medullary cells into the spinal subarachnoid space may produce antinociception via inhibition of spinal pain transmission pathways, alterations at higher central nervous system (CNS) centers have not been addressed. Recent findings suggest that prolonged noxious stimulation results in release of endogenous beta-endorphin in the brain, possibly as a compensatory mechanism to reduce nociception. The goal of this study was to determine whether adrenal medullary transplants in the spinal subarachnoid space alter endogenous beta-endorphin secretion in the hypothalamic arcuate nucleus, its principal CNS source. Pain behaviors and arcuate beta-endorphin secretion by microdialysis were monitored during the formalin pain test in animals with spinal adrenal medullary or control transplants. Basal levels of extracellular beta-endorphin were 3-fold higher in adrenal medullary-implanted than in controls. In control animals, formalin induced robust pain behaviors and a marked transient increase in beta-endorphin release 30-60 min following injection. In contrast, pain behaviors were attenuated and the formalin-induced increase in beta-endorphin was completely blocked in adrenal medullary implanted animals. Findings from these studies indicate that adrenal medullary transplants in the spinal subarachnoid space can alter beta-endorphin release in the arcuate nucleus both basally and in response to noxious stimuli. Thus, spinally placed adrenal medullary transplants not only alter local spinal cord pharmacology, but can alter endogenous neurochemistry at higher pain processing centers as well.

Topics: Adrenal Medulla; Analgesia; Animals; Arcuate Nucleus of Hypothalamus; Behavior, Animal; beta-Endorphin; Male; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Spinal Cord; Subarachnoid Space; Tissue Transplantation

CNS correlates of acute prolonged pain, and the effects of partial blockade of the central beta-endorphin system, were investigated by the quantitative 2-deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin-induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti-beta-endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin-injected rats, pretreated with anti-beta-endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo-cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for beta-endorphin in central networks that process somatosensory inputs.

Topics: Animals; Antibodies; Antimetabolites; Behavior, Animal; beta-Endorphin; Blood Glucose; Central Nervous System; Deoxyglucose; Disinfectants; Formaldehyde; Grooming; Injections, Intraventricular; Male; Pain; Rabbits; Rats; Rats, Sprague-Dawley; Software

The aim of the present study was to investigate the effect of somatostatin administration in arthritic rats. Inflammation was induced by daily interplantar injection of 100 microl of Freund's complete adjuvant into the left hind paw of the rat. Arthritis developed 20 days following the first injection and was stable in the inoculate paw. Arthritic rats were treated interplantarly with somatostatin (5 or 10 microg) or with indomethacin (100 microg) daily for 14 days. Inflammatory response was studied at 12 h, 7 and 14 days following drug administration. The effect of somatostatin was determined by local (into popliteal lymph nodes) and systemic production of beta-endorphin. Our results showed that somatostatin treatment significantly increased beta-endorphin levels in the blood and lymphocytes from popliteal lymph nodes. Greater efficiency was seen when 5 microg instead of 10 microg of somatostatin was used. A significant decrease of absolute leukocytosis was observed at the 14th day following somatostatin administration. Moreover, a significant reduction of plasmatic beta-globulins at 12 h and the 7th day and of plasmatic alpha2-globulins at the 14th day was observed after the beginning of somatostatin treatment.

Topics: Alpha-Globulins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; beta-Endorphin; Beta-Globulins; Chronic Disease; gamma-Globulins; Indomethacin; Inflammation; Male; Pain; Rats; Rats, Wistar; Somatostatin

In this study, we attempted to clarify the correlation between changes in the level of beta-endorphin (beta-EP) in the mouse brain and the stress-induced analgesia (SIA) after exposing animals to forced walking stress. The immunohistochemical distribution of beta-EP after stress was first analyzed quantitatively in mice and then more specifically using a microphotometry system with results showing that the fluorescence intensity of beta-EP in the peri-aqueductal gray matter (PAG) and arcuate nucleus of the medial basal hypothalamus (ARC) was increased 6 h after exposure to forced walking stress. Further, SIA was examined after exposing animals to the forced walking stress and the formalin test. At 6 h after forced walking stress, significant SIA was observed in the second phase (from 10 to 30 min after formalin injection) of the formalin-induced paw licking behavior, but not in the first phase (from 0 to 10 min after formalin injection). This SIA was antagonized by beta-EP-(1-27), an opioid epsilon receptor antagonist. In nonstressed mice, the injection of beta-EP produced a reduction in formalin-induced paw-licking in the second phase. A significant antinociceptive effect by beta-EP was well antagonized by beta-EP-(1-27). Thus, the present results suggest that the increase in beta-EP levels in PAG and/or ARC may be involved in SIA after exposure of mice to the forced walking stress.

Topics: Analgesia; Animals; Behavior, Animal; beta-Endorphin; Brain; Formaldehyde; Humans; Male; Mice; Pain; Pain Measurement; Physical Exertion; Stress, Physiological; Walking

Although the involvement of both endogenous opioid and serotonergic systems in modulation of pain and emotion was suggested, the neurochemical interaction between these systems in the brain has not previously been studied directly. Herein, the effects of the local application of serotonin (5-HT) and fluoxetine (a 5-HT reuptake inhibitor) on extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens were assessed in freely moving rats using in vivo microdialysis. The mean basal concentrations of beta-endorphin in dialysates obtained from the arcuate nucleus and nucleus accumbens were 259.9 and 143.3 pM, respectively. Specific lesion of the serotonergic system by 5,7-dihydroxytryptamine (5,7-DHT) caused a significant decrease in these dialysate beta-endorphin levels. When 5-HT (0.25-5 microM) was added to the perfusion solution, the levels of beta-endorphin in the dialysate from the arcuate nucleus increased (186-296% of baseline), in a concentration-dependent manner. In the nucleus accumbens, 0.5 and 2 microM 5-HT in the perfusion fluid did not affect the levels of beta-endorphin in the dialysate, whereas 5 and 10 microM 5-HT caused an increase of approximately 190% of baseline. When fluoxetine (250 microM) was present in the perfusing solution, the levels of beta-endorphin in the dialysates from the arcuate nucleus and nucleus accumbens increased two- to threefold. This effect was not obtained in the 5,7-DHT-lesioned rats. Thus, 5-HT, either endogenously or exogenously delivered, appears to facilitate the release of beta-endorphin in the arcuate nucleus and nucleus accumbens. This indication of an interaction between serotonergic and endorphinic systems may be relevant for assessing pain and mood disorder circuits and the mode of action of antidepressant drugs.

Topics: 5,7-Dihydroxytryptamine; Affect; Animals; Antidepressive Agents; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Emotions; Extracellular Space; Fluoxetine; Male; Microdialysis; Nucleus Accumbens; Pain; Rats; Rats, Sprague-Dawley; Reward; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Agents

The effect of total saponin fraction of ginseng injected intrathecally (i.t.) or intracerebroventricularly (i.c.v.) on the antinociception induced by beta-endorphin administered i.c.v. was studied in ICR mice in the present study. The antinociception was assessed by the tail-flick test. Total saponin fraction at doses 0.1 to 1.0 microgram, which administered i.t. alone did not affect the latencies of tail-flick threshold, attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin (1 microgram). However, total saponin fraction at doses 1 to 20 microgram, which administered i.c.v. alone did not affect the latencies of the tail-flick response, did not affect i.c.v. administered beta-endorphiun (1 microgram)-induced antinociception. The duration of antagonistic action of total saponin fraction against beta-endorphin-induced antinociception lasted at least for 6 h. Various doses (from 0.1 to 1 microgram) of ginsenoside R(c), but not R(b2), R(d), Rg(1), R(b1)and R(e)injected i.t. dose-dependently attenuated antinociception induced by beta-endorphin administered i.c.v. Our results indicate that total saponin fraction injected spinally appears to have antagonistic action against the antinociception induced by supraspinally applied beta-endorphin. Ginsenoside R(c)appears to be responsible for blocking i.c.v. administered beta-endorphin-induced antinociception. On the other hand, total ginseng fraction, at supraspinal sites, may not exert an antagonistic action against the antinociception induced by supraspinally administered beta-endorphin.

Topics: Analgesics; Animals; beta-Endorphin; Central Nervous System Agents; Cerebral Ventricles; Ginsenosides; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Pain; Panax; Plants, Medicinal; Saponins; Spinal Cord; Time Factors

The present study was designed to investigate the modulatory effects of blockade of spinal histamine receptors on antinociception induced by supraspinally administered mu-epsilon-, delta-, and kappa-opioid receptor agonists. The effects of intrathecal (i.t.) injections with cyproheptadine [a histamine-1 (H1) receptor antagonist], ranitidine (a H2 receptor antagonist), or thioperamide (a H3 receptor antagonist) injected i.t., on the antinociception induced by morphine (a mu-receptor antagonist), beta-endorphin (an epsilon-receptor agonist), D-Pen(2,5)-enkephalin (DPDPE, a delta-receptor agonist) or trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohxyl] benzeocetamide (U50,488H, a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick test. The i.t. injection of cyproheptadine (from 0.31 to 62 nmole), ranitidine (from 0.28 to 56 nmole), or thioperamide (from 0.24 to 48 nmole) alone did not show any antinociceptive effect. The i.t. pretreatment with cyproheptadine or thioperamide dose-dependently attenuated the inhibition of the tail-flick response induced by i.c.v. administered morphine (0.6 nmole), b-endorphin (0.03 nmole), DPDPE (1.5 nmole), and U50,488H (130 nmole). In addition, the i.t. pretreatment with ranitidine dose-dependently attenuated the inhibition of the tail-flick response induced by morphine, b-endorphin and U50,488H without affecting DPDPE-induced response. Our results suggest that spinal histamine H1 and H3 receptors may involved in the production of antinociception induced by supraspinally applied morphine, b-endorphin, DPDPE and U50,488H. Spinal H2 receptors appear to be involved in supraspinally administered morphine, b-endorphin- and U50,488H-induced antinociception but not DPDPE-induced antinociception.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; beta-Endorphin; Cerebral Ventricles; Cyproheptadine; Enkephalin, D-Penicillamine (2,5)-; Histamine Antagonists; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Morphine; Pain; Piperidines; Ranitidine; Receptors, Histamine H1; Receptors, Histamine H2; Receptors, Histamine H3; Receptors, Opioid; Spinal Cord

The hypothesis that the naturally occurring analgesic peptide, beta-endorphin, is released in the brain in response to pain had never been directly validated. In this study, we applied a brain microdialysis method for monitoring beta-endorphin release in vivo, to test this hypothesis in the brains of conscious, freely moving rats. Herein we first show that endogenous beta-endorphin can be measured in vivo in the brain under physiological conditions. Upon induction of a nociceptive stimulus by injection of formalin into the hind-paws of rats, the extracellular levels of beta-endorphin in their arcuate nucleus increased by 88%, corresponding to their nociceptive response. This direct evidence for the release of endogenous beta-endorphin in the brain in response to nociceptive stimulus indicates a possible mechanism for organisms to cope with pain.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Formaldehyde; Male; Microdialysis; Nociceptors; Pain; Potassium Chloride; Rats; Rats, Sprague-Dawley

Topics: Animals; beta-Endorphin; Corticotropin-Releasing Hormone; Inflammation; Pain; Rats; Stress, Psychological; T-Lymphocytes

This study was designed to evaluate the potential advantages of combined epidural and light general anesthesia over the commonly employed general anesthesia during open heart surgery. Twenty-four patients undergoing mitral valve replacement were thus studied. General anesthesia was maintained with an isoflurane-nitrous oxide-oxygen was mixture and morphine sulfate (0.4 mg/kg i.v. initially) followed by postoperative pain control with morphine in 12 patients (group GA). The remaining 12 patients (group EAA) received continuous epidural bupivacaine (0.125%)-morphine (50 micrograms/ml) supplemented with the same gas mixture as group GA. Epidural infusion was continued until the third postoperative day. Changes in the serum cortisol and beta-endorphin levels together with postoperative pain relief defined as good (scale 0-2), fair (3-4), or poor (5-10) were observed serially. Lower cortisol levels were observed in group EAA than in group GA (P < 0.05) just before skin closure, on the second and the third postoperative day. The beta-endorphin levels were substantially lower in group EAA than in group GA throughout the observation. The pain scores were good in 2 patients (17%), fair in 6 (50%), and poor in 4 (33%) for group GA, and good in 8 (67%), fair in 3 (25%), and poor in 1 (8%) for group EAA. We thus conclude that a combined epidural and light general anesthesia is considered to attenuate the stress response and thereby provides a better quality of postoperative pain control.

Topics: Adult; Analgesics, Opioid; Anesthesia, Epidural; Anesthesia, Inhalation; Anesthetics, Inhalation; beta-Endorphin; Cardiac Surgical Procedures; Female; Humans; Hydrocortisone; Isoflurane; Male; Mitral Valve Stenosis; Morphine; Nitric Oxide; Oxygen; Pain; Postoperative Complications

Recent research indicates that the sensitization that results from repeated drug or non-drug stress exposure may develop into a pattern of alternating increases and decreases (i.e., oscillation) in response to each subsequent stressor exposure. Oscillation, with or without prior sensitization, has been observed for a number of drug and non-drug stressors, and for various neurochemical and endocrine endpoints. The present studies investigated whether oscillation also occurs in the behavioral and endocrine effects of repeated morphine treatment and if a drug that normalizes the mood swings of bipolar disorder in humans will also attenuate drug oscillation in this animal model. In the first experiment, rats were given 1-5 pretreatments with morphine (15 mg/kg, i.p.), separated by 1-week intervals with the last injection occurring 1 hour prior to being tested for stressor-induced (i.e., 5 seconds, 2-mA electric footshock) hypoalgesia, as measured by latency to paw-lift or jump from a hot-plate. Plasma beta-endorphin also was measured. The second experiment replicated the behavioral findings of the first study and, in addition, assessed the effect of continuous lithium chloride, in the drinking water, on morphine-induced oscillation. Caffeine was used as a partial control for the lithium. The results were that one injection of morphine enhanced stress-induced hypoalgesia and subsequent morphine administrations resulted in oscillation. Beta-endorphin exhibited sensitization but not oscillation, suggesting that it did not mediate oscillation of the behavioral response. In addition, lithium, but not caffeine, eliminated oscillations of the behavioral response without affecting its initial enhancement.

Topics: Analysis of Variance; Animals; beta-Endorphin; Caffeine; Electroshock; Lithium Chloride; Male; Morphine; Oscillometry; Pain; Rats; Rats, Sprague-Dawley

Topics: Analgesia; Animals; beta-Endorphin; Cell Movement; Drug Design; Humans; Immune System; Inflammation; Nociceptors; Pain; Selectins

Opioid-containing immune cells migrate preferentially to inflamed sites, where they release beta-endorphin which activates peripheral opioid receptors to inhibit pain. Immunocyte recruitment is a multistep, sequential engagement of various adhesion molecules located on immune cells and vascular endothelium. Selectins mediate the initial phase of immunoctye extravasation into inflamed sites. Here we show that anti-selectin treatment abolishes peripheral opioid analgesia elicited either endogenously (by stress) or by corticotropin-releasing factor. This results from a blockade of the infiltration of immunocytes containing beta-endorphin and the consequent decrease of the beta-endorphin content in the inflamed tissue. These findings indicate that the immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain in injured tissue. Thus, pain is exacerbated by measures inhibiting the immigration of opioid-producing cells or, conversely, analgesia might be conveyed by adhesive interactions that recruit those cells to injured tissue.

Topics: Analgesia; Animals; beta-Endorphin; Cell Movement; Corticotropin-Releasing Hormone; Drug Design; Immune System; Inflammation; Male; Nociceptors; Pain; Polysaccharides; Radioimmunoassay; Rats; Rats, Wistar; Selectins; Sulfuric Acid Esters

Localized inflammation of a rat's hindpaw elicits an accumulation of beta-endorphin-(END) containing immune cells. We investigated the production, release, and antinociceptive effects of lymphocyte-derived END in relation to cell trafficking. In normal animals, END and proopiomelanocortin mRNA were less abundant in circulating lymphocytes than in those residing in lymph nodes (LN), suggesting that a finite cell population produces END and homes to LN. Inflammation increased proopiomelanocortin mRNA in cells from noninflamed and inflamed LN. However, END content was increased only in inflamed paw tissue and noninflamed LN-immune cells. Accordingly, corticotropin-releasing factor and IL-1beta released significantly more END from noninflamed than from inflamed LN-immune cells. This secretion was receptor specific, calcium dependent, and mimicked by potassium, consistent with vesicular release. Finally, both agents, injected into the inflamed paw, induced analgesia which was blocked by the co-administration of antiserum against END. Together, these findings suggest that END-producing lymphocytes home to inflamed tissue where they secrete END to reduce pain. Afterwards they migrate to the regional LN, depleted of the peptide. Consistent with this notion, immunofluorescence studies of cell suspensions revealed that END is contained predominantly within memory-type T cells. Thus, the immune system is important for the control of inflammatory pain. This has implications for the understanding of pain in immunosuppressed conditions like cancer or AIDS.

Topics: Analysis of Variance; Animals; beta-Endorphin; Corticotropin-Releasing Hormone; Freund's Adjuvant; Hindlimb; Humans; Inflammation; Interleukin-1; Lymph Nodes; Male; Pain; Pro-Opiomelanocortin; Rats; Rats, Wistar; Regression Analysis; RNA, Messenger; T-Lymphocytes; Time Factors; Transcription, Genetic

Mice made cold water swimming (CWS: 4 degrees C, 3 min) produced an opioid-mediated antinociception. Experiments were designed to determine what types of opioid receptors and endogenous opioid peptides in the spinal cord are involved in the CWS-induced antinociception in male ICR mice. Antinociception was measured by the tail-flick test. CWS-induced antinociception was blocked by intrathecal (i.t.) pretreatment with antiserum to [Met5]enkephalin (100 microg, 1 hr), but not by antiserum (100 microg, 1 hr) to [Leu5]enkephalin, beta-endorphin or dynorphin A (1-17). Moreover, i.t. pretreatment with delta2-opioid receptor antagonist naltriben (NTB: 10 microg, 10 min) blocked the antinociception induced by CWS or i.t.-administered [Met5]enkephalin (10 microg). However, the antinociception induced by CWS or i.t.-administered [Met5]enkephalin was not blocked by i.t. pretreatment with delta1-opioid receptor antagonist 7-benzylidene naltrexone (BNTX: 1 microg, 10 min), mu-opioid receptor antagonist D-Phe-Cys-Try-D-Try-Om-Thr-Phe-Thr-NH2 (CTOP: 50 ng, 10 min), or kappa-opioid receptor antagonist norbinaltorphimine (norBNI: 5 microg, 24 hr). These data indicate that [Met5]enkephalin and delta2-opioid receptor in the spinal cord are involved in antinociception induced by CWS.

Topics: Animals; beta-Endorphin; Cold Temperature; Dynorphins; Enkephalin, Leucine; Enkephalin, Methionine; Immune Sera; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Pain; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Spinal Cord

Topics: Animals; beta-Endorphin; Immunohistochemistry; Inflammation; Pain; Pro-Opiomelanocortin; Radioimmunoassay; Rats; RNA, Messenger; T-Lymphocytes

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms.

Topics: Amino Acid Sequence; Analgesia; Analgesics, Opioid; Animals; Base Sequence; beta-Endorphin; Circadian Rhythm; Codon; DNA Primers; Female; Hypothalamo-Hypophyseal System; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Morphine; Mutagenesis, Site-Directed; Naloxone; Pain; Pituitary-Adrenal System; Polymerase Chain Reaction; Pro-Opiomelanocortin; Protein Biosynthesis; Sex Characteristics; Stem Cells; Stress, Psychological; Tyrosine

The effect of nicotine administered supraspinally on antinociception induced by supraspinally administered opioids was examined in ICR mice. The intracerebroventricular (i.c.v.) injection of nicotine alone at doses from 1 to 12 micrograms produced only a minimal inhibition of the tail-flick response. Morphine (0.2 micrograms), beta-endorphin (0.1 microgram), D-Pen2.5-enkephalin (DPDPE; 0.5 microgram), trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide (U50, 488H; 6 micrograms) caused only slight inhibition of the tail-flick response. Nicotine dose dependently enhanced inhibition of the tail-flick response induced by i.c.v. administered morphine (0.2 microgram) or beta-endorphin (0.1 microgram). The degree of enhancing effect of nicotine toward beta-endorphin-induced inhibition of the tail-flick response was greater than toward morphine-induced inhibition of the tail-flick response. However, i.c.v. administered nicotine at the same doses was not effective in enhancing the inhibition of the tail-flick response induced by DPDPE (0.5 microgram) or U50, 488H (6 micrograms) administered i.c.v. Our results suggest that stimulation of supraspinal nicotinic receptors may enhance antinociception induced by morphine (a mu-opioid receptor agonist) and beta-endorphin (an epsilon-opioid receptor agonist) administered supraspinally. However, the activation of nicotinic receptors at supraspinal sites may not be involved in enhancing the antinociception induced by DPDPE (a delta-opioid receptor agonist) or U50, 488H (a kappa-opioid receptor agonist) administered supraspinally.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; beta-Endorphin; Drug Synergism; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Morphine; Nicotine; Nociceptors; Pain; Pain Measurement; Pyrrolidines; Receptors, Opioid, delta; Receptors, Opioid, kappa

The present study was designed to investigate the modulatory effects of blockade of spinal histamine receptors on antinociception induced by spinally administered morphine, beta-endorphin and U50, 488H. The effects of intrathecal (i.t.) injections with cyproheptadine (a histamine-1 (H1) receptor antagonist), ranitidine (an H2 receptor antagonist), or thioperamide (an H3 receptor antagonist) injected i.t., on the antinociception induced by morphine, beta-endorphin or trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide (U50, 488H) injected intrathecally (i.t.) were studied. The antinociception was assayed using the tail-flick test. The i.t. injection of cyproheptadine (20 micrograms), ranitidine (20 micrograms), or thioperamide (20 micrograms) alone did not produce any antinociceptive effect. i.t. pretreatment with cyproheptadine attenuated the inhibition of the tail-flick response induced by i.t. administered morphine or beta-endorphin, but not U50, 488H. In addition, i.t. pretreatment with ranitidine attenuated the inhibition of the tail-flick response induced by i.t. administered morphine, beta-endorphin, or U50, 488H. Furthermore, the i.t. pretreatment with thioperamide attenuated the inhibition of the tail-flick response induced by beta-endorphin or U50, 488H, but not morphine, administered i.t. Our results indicate that spinal H1 receptors may be involved in the production of antinociception induced by spinally applied morphine or beta-endorphin- but not U50, 488H. Spinal H2 receptors appear to be involved in spinally administered morphine-, beta-endorphin- and U50, 488H-induced antinociception. Supraspinal histamine H3 receptors may be involved in the production of antinociception induced by supraspinally applied beta-endorphin or U50, 488H, but not morphine.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; beta-Endorphin; Cyproheptadine; Histamine H1 Antagonists; Histamine H2 Antagonists; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Morphine; Pain; Pain Measurement; Piperidines; Pyrrolidines; Ranitidine; Receptors, Histamine H1; Receptors, Histamine H2; Receptors, Histamine H3; Spinal Cord

The behavioral and immunoendocrine effects of formalin-induced pain were studied in male rats following a subcutaneous injection of formalin (50 microliters; 0.1%, F01 groups, 10%, F10 groups) or sham injection (control groups). After treatment, animals were tested in a transparent open field for either 30 or 60 min and thereafter sacrificed by decapitation. Plasma was collected for adrenocorticotropic hormone (ACTH), corticosterone, beta-endorphin (beta-EP) and interleukin-6 (IL-6) determinations. Pain-evoked responses (licking, flexing, paw jerk), standard measures of activity (locomotion, rearing, olfactory exploration) and self-grooming were recorded. The higher formalin concentration induced stronger pain-evoked behavioral responses, paralleled by higher levels of ACTH, beta-EP and IL-6, but did not affect the other behavioral parameters. In contrast, the lower formalin concentration induced a marked increase in locomotion and rearing and a decrease in ACTH levels. In both formalin-injected groups, corticosterone did not differ from controls.

Topics: Adrenocorticotropic Hormone; Animals; Behavior, Animal; beta-Endorphin; Corticosterone; Formaldehyde; Interleukin-6; Male; Pain; Rats; Rats, Wistar; Time Factors

To investigate whether duodenal ulcer patients with painful active peptic ulcer and those with silent active ulceration have different plasma beta-endorphin levels.. Forty-five patients (28 men and 17 women), aged 38-50 years, with at least a 5-year history of duodenal ulceration. Twenty-two patients had painful symptoms, while 23 had silent active duodenal ulcer.. Beta-endorphin plasma levels (pmol/l) were measured during an acute episode of duodenal ulcer, before and after antisecretory therapy with omeprazole. In three patients we measured the concentration of beta-endorphin in gastric juice before and after pentagastric (6 micrograms/kg subcutaneous) stimulation.. The basal values of beta-endorphin in both patients with asymptomatic and those with symptomatic duodenal ulcer showed no difference before or after 30 days of antisecretory treatment. Plasma beta-endorphin levels (median values in the normal range < 12 pmol/l) were significantly higher (Student's t-test, P < 0.005) in the asymptomatic than in symptomatic patients, both before (9.07 +/- 4.8 versus 5.6 +/- 2.5 pmol/l) and after (8.7 +/- 4.1 versus 5.7 +/- 2.4 pmol/l) omeprazole treatment. The highest levels of beta-endorphin were found in four patients with a negative history for any pain symptom (visual analogue scale score 0).. Our data suggest that the opioid system, particularly beta-endorphin, is involved in the perception of pain in duodenal ulcer disease, which explains the silent clinical characteristics of some peptic ulcers. In addition, the concentration of beta-endorphin found in gastric juice indicates a possible peripheral effect of this opiate.

Topics: Adult; beta-Endorphin; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Nociceptors; Omeprazole; Pain

Although a hypertension-related hypalgesia has been described, the relation between pain perception and the 24-hour blood pressure trend is still unknown. The ambulatory blood pressure monitoring parameters and dental pain sensitivity were correlated in 67 male subjects. The pulpar test (graded increase of test current of 0 to 0.03 mA) was performed on three healthy teeth, and mean dental pain threshold (occurrence of pulp sensation) and pain tolerance (time when the subjects asked for the test to be stopped) were evaluated. Three groups of subjects with normal (n = 34), intermediate (n = 13), and high (n = 20) blood pressure values were identified according to ambulatory monitoring results. Pain threshold differed among the three groups (P < .02), being higher in the group with highest blood pressure. The groups of hypertensive subjects showed higher pain tolerance than the normotensive group (P < .02). Pain threshold was correlated with 24-hour, diurnal, and nocturnal blood pressure values. Pain tolerance was also related to 24-hour blood pressure and to diurnal and nocturnal diastolic and mean arterial pressure values. Systolic and diastolic blood pressure loads were significantly associated with pain threshold, and diastolic load was also associated with tolerance. The blood pressure variability (SD) did not relate to pain perception. The 24-hour arterial pressure was more closely associated with pain perception than the blood pressure values obtained before the pulpar test. A close correlation between pain perception and 24-hour ambulatory blood pressure was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta-Endorphin; Blood Pressure Monitoring, Ambulatory; Humans; Male; Middle Aged; Pain; Pain Measurement; Perception; Sensory Thresholds

The purpose of this study was to assess whether xenogeneic tumor cells immunologically isolated in polymer capsules could survive and continue to reduce pain when transplanted into the cerebrospinal fluid (CSF) of rats. The mouse tumor cell lines AtT-20 and gene-transfected Neuro2A, which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5 x 10(6) cells/ml and transplanted into the spinal CSF space of the occipitoatlantal junction in male Sprague-Dawley rats. The analgesiometric tests (tail pinch, hot plate, and electrical stimulation) showed that the five rats with encapsulated AtT-20 or Neuro2A (eight rats) were significantly less sensitive to pain after transplantation than the eight control animals (analysis of variance; p < 0.05). The analgesia induced by encapsulated cells secreting beta-endorphin could be attenuated by the opiate antagonist naloxone, which suggested the involvement of opiate in mediating this response. Morphological study revealed that the cells in polymer capsules survived 1 month after transplantation in the CSF space. In vitro experiments with cultured capsules showed that both encapsulated AtT-20 and Neuro2A secrete peptide for 1 month. The results of this study suggest that immunologically isolated xenogeneic tumor cells can secrete opiate in the CSF space, and this method may be applied to the treatment of cancer pain.

Topics: Analgesia; Animals; beta-Endorphin; Capsules; Cell Aggregation; Male; Mice; Neoplasm Transplantation; Neuroblastoma; Pain; Pain Measurement; Pituitary Neoplasms; Polymers; Prostheses and Implants; Rats; Rats, Sprague-Dawley; Subarachnoid Space; Tumor Cells, Cultured

To examine the resting and evoked release of the endogenous opioid peptides beta-endorphin and Met-enkephalin from brain, we examined the levels of the respective immunoreactivities in the lateral ventricle-cisterna magna perfusate of the halothane-anesthetized rat. Ten Hz but not 100 Hz stimulation in the arcuate nucleus (ARC) of the hypothalamus released beta-endorphin immunoreactivity (beta-EPir) to the perfusate, whereas 100 Hz but not 10 Hz stimulation in the periaqueductal gray (PAG) of the mid brain released Met-enkephalin immunoreactivity (MEir). MEir was not released by stimulation in ARC and beta-EPir was not released by stimulation in PAG. Characterization of the released beta-EPir and MEir by high performance liquid chromatography showed that authentic beta-endorphin and Met-enkephalin were the major constituents of beta-EPir and MEir, respectively. Systemic administration of the dopaminergic antagonist haloperidol increased plasma, but not perfusate levels of beta-EPir. Both the opioid antagonist naloxone and the NMDA antagonist MK-801 failed to affect beta-EPir or MEir release. ARC and PAG stimulated inhibited a nociceptive reflex (tail-dip in 52.5 degrees C water), and naloxone did not reliably reverse this inhibition. These data support the previously suggested possibility of opioid mediation of stimulation induced analgesia, although we were unable to confirm the theory by naloxone reversibility in this study. Furthermore, the data support the assumption that measurement of opioid peptides in cerebrospinal fluid is a relevant approach in research aimed at elucidating the physiological and pathophysiological roles of endogenous opioid peptides.

Topics: Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Cerebral Ventricles; Cisterna Magna; Electric Stimulation; Enkephalin, Methionine; Immunohistochemistry; Male; Pain; Pain Measurement; Perfusion; Periaqueductal Gray; Rats; Rats, Sprague-Dawley; Reflex

Repetitive exposure of rats to a hot plate induced a novel non-opioid form of stress induced analgesia. The exposure caused a persistent 1.5-2 s increase in tail flick latency which was not attenuated by systemic naltrexone, but was completely inhibited by systemic MK-801. Concomitantly, alterations occurred in the ability to pharmacologically distinguish multiple beta-endorphin receptors in the periaqueductal gray. Thus, in response to different forms of stress, different pathways may be activated by beta-endorphin, resulting in stress induced analgesias with varied pharmacological characteristics (e.g., opioid and non-opioid).

Topics: Amino Acid Sequence; Analgesia; Animals; beta-Endorphin; Cytidine Triphosphate; Dizocilpine Maleate; Heating; Male; Microinjections; Molecular Sequence Data; Morphine; Narcotic Antagonists; Pain; Periaqueductal Gray; Rats; Rats, Sprague-Dawley; Stress, Physiological; Synaptic Transmission

Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides.

Topics: Analysis of Variance; Animals; Antibodies; beta-Endorphin; Corticotropin-Releasing Hormone; Cyclosporine; Dose-Response Relationship, Drug; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Humans; Inflammation; Injections; Interleukin-1; Male; Naloxone; Pain; Rats; Rats, Wistar; Recombinant Proteins; Regression Analysis; Somatostatin

The purpose of this study was to investigate whether the fetus mounts a hormonal stress response to a potentially painful procedure, intrauterine needling. Cortisol and beta-endorphin concentrations in fetal plasma obtained during uncomplicated fetal blood sampling or intrauterine transfusions by needling the fetal intra-abdominal portion of the umbilical vein (intrahepatic vein) were compared to hormone concentrations in fetal plasma obtained by the conventional technique of needling the placental cord insertion, which is not innervated. Cortisol and beta-endorphin concentrations did not increase within 10 minutes of fetal abdominal needling (n = 15). However, more prolonged needling during transfusion at the intrahepatic vein was associated with an increase in fetal plasma cortisol (median increase 48 nmol/L; 95% Cl, 23-86) and beta-endorphin (207 pg/mL; 113-307) concentrations compared to transfusion at the placental cord insertion (p < 0.005 for both hormones). The magnitude of rise in hormone increased linearly with the duration of needling (cortisol, r = 0.80; beta-endorphin, r = 0.88, p < 0.05 for both). These data suggest that the fetus mounts a hormonal stress response to invasive procedures. They raise the possibility that the human fetus feels pain in utero, and may benefit from anaesthesia or analgesia for invasive procedures.

Topics: Analgesia; beta-Endorphin; Blood Transfusion, Intrauterine; Carbon Dioxide; Chromatography, High Pressure Liquid; Cordocentesis; Female; Fetal Blood; Fetus; Gestational Age; Humans; Hydrocortisone; Oxygen; Pain; Pregnancy; Prospective Studies; Radioimmunoassay; Stress, Physiological; Time Factors

Topics: Abortion, Induced; beta-Endorphin; Female; Fetus; Humans; Hydrocortisone; Pain; Pain Measurement; Pregnancy; Sensation

Chlornaltrexamine (beta-CNA, 0.5 micrograms) alone or beta-CNA plus either mu-agonist, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO, 500 ng) or delta-agonist, D-Pen2-D-Pen5-enkephalin (DPDPE, 10 micrograms) was injected intrathecally (i.t.) to protect mu- or delta-opioid receptors, respectively, for 24 h in male ICR mice. The antinociception was assessed by the tail-flick and hot-plate test. DPDPE or DAMGO injected i.t. increased inhibition of the tail-flick and hot-plate response in a dose-dependent manner. The dose-response curve for tail-flick and hot-plate response induced by DPDPE or DAMGO in i.t. saline-treated group significantly shifted to the right in i.t. beta-CNA alone treated group but returned to the control level in the group treated with i.t. beta-CNA coadministered with DPDPE or DAMGO, respectively. The effects of protection of mu- and delta-opioid receptor in the spinal cord on inhibition of the tail-flick and hot-plate response induced by beta-endorphin and morphine administered intracerebroventricularly (i.c.v.) were then studied. Intrathecal pretreatment with beta-CNA or beta-CNA coadministered with DAMGO attenuated inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. However, i.t. treatment with beta-CNA coadministered with DPDPE did not affect inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. Intrathecal pretreatment with beta-CNA or beta-CNA coadministered with either DPDPE or DAMGO did not alter inhibition of the hot-plate response induced by beta-endorphin administered i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Sequence; Analgesics; Animals; beta-Endorphin; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Molecular Sequence Data; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Spinal Cord

These studies were designed to investigate how the aging process alters the spinal antinociceptive efficacy of mu (mu), delta (delta) and epsilon (epsilon) opioid receptor agonists administered intrathecally (i.t.) in rats. Various doses of the mu agonist DAGO, the delta agonist DPDPE or the putative epsilon beta-endorphin were injected i.t. in young (5-6-month-old), mature (15-16-month-old) and aged (25-26-month-old) Fischer 344 rats. Antinociception was measured using the rat tail-flick analgesiometric assay. The data demonstrated a decline in spinal opioid-induced antinociception as a function of age. For instance, the i.t. dose of DPDPE or beta-endorphin needed to produce antinociception in the 25-26-month-old rats was higher than that needed to elevate tail-flick latency in the young and mature animals. We also noted that the i.t. doses of the opioid agonists needed to produce 'antinociception' in the aged cohort were within a range of spinal doses that produced motor impairment. Apparently, the aging process alters the ability of opioid receptors to mediate antinociception. Perhaps an age-related decrease in the number and/or affinity of opioid receptor sites in the rat spinal cord accounts for these observations.

Topics: Aging; Analgesics; Analysis of Variance; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Injections, Spinal; Male; Pain; Rats; Rats, Inbred F344; Spine

A polyclonal antiserum directed against the first 16 amino acids of the N-terminal sequence of the murine delta opioid receptor was raised in rabbits. The intracerebroventricular (i.c.v.) injection to mice of the anti delta receptor IgGs impaired the antinociception produced by DPDPE, [D-Ala2]-Deltorphin II, DADLE and beta-endorphin-(1-31) when studied 24 h later in the tail-flick test. Antinociception produced by morphine and DAMGO was fully expressed in mice undergoing this treatment. The selective delta antagonist ICI 174864 (0.8 nmols/mouse, i.c.v.) significantly reduced the antinociceptive activity of opioids to the extent observed after giving the antibodies. ICI 174864 did not decrease further the antinociception that remained after the anti delta receptor serum. The specific binding displayed by 3 nM [3H]-DPDPE was reduced in membranes pre-incubated with the antiserum, whereas no change could be detected for 0.6 nM [3H]-DAMGO labelling mu receptors. This experimental approach revealed the delta component of opioid-evoked supraspinal antinociception in mice.

Topics: Amino Acid Sequence; Analysis of Variance; Animals; beta-Endorphin; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; GTP-Binding Proteins; Immunoglobulin G; Immunohistochemistry; Male; Mice; Mice, Inbred Strains; Molecular Sequence Data; Morphine; Narcotic Antagonists; Oligopeptides; Pain; Pain Measurement; Protein Binding; Reaction Time; Receptors, Opioid, delta

We investigated whether the anti-aversive effects of salmon calcitonin (SCT) was induced by increasing ACTH and beta-endorphin and/or by decreasing of prostaglandin E2 (PGE2) levels in plasma of mice to elucidate the mechanisms responsible for the analgesic effects of SCT. Intracerebroventricular (i.c.v.) injections of SCT inhibited acetic acid-induced aversive behavior (writhing) in a U-shaped dose response curve, the most effective dose being 0.1 IU/mouse. Intraperitoneal (i.p.) injections of acetic acid increased, but not significantly, the levels of plasma ACTH and PGE2, but not beta-endorphin, which are considered to be psychoneuroendocrines correlated with pain. SCT (0.1 IU/mouse, i.c.v.) significantly increased plasma ACTH levels (p < 0.05) and tended to increase beta-endorphin levels (p = 0.052) in acetic acid-treated mice, whereas no change in PGE2 level was observed (p > 0.1). These results suggest that the anti-aversive effects of SCT may be mediated, at least in part, by the activation of ACTH.

Topics: Acetates; Acetic Acid; Adrenocorticotropic Hormone; Analgesics; Animals; beta-Endorphin; Calcitonin; Dinoprostone; Male; Mice; Pain; Radioimmunoassay

Pharmacological evidence for the existence of delta-opioid receptor subtypes has been reported. This study was conducted to determine which type of delta-opioid receptors was involved supraspinally and spinally when antinociception was induced by the natural enkephalins, [Leu5]enkephalin and [Met5]enkephalin. In the mouse tail flick assay, the antinociceptive ED50 values of both intracerebroventricularly (i.c.v.) administered [Leu5]enkephalin and [Met5]enkephalin (together with the peptidase inhibitors, bestatin and thiorphan) were significantly increased by 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist but not by naltriben, a selective delta 2-opioid receptor antagonist. On the other hand, when the enkephalins were administered intrathecally (i.t.), the antinociceptive ED50 values of both enkephalins were significantly raised by naltriben but not by BNTX. beta-Endorphin-induced (i.c.v.) antinociception was antagonized by naltriben administered i.t. or s.c. but not by BNTX administered i.t. or s.c. Different delta-opioid receptor subtypes appeared to be involved in supraspinal (delta 1) and spinal (delta 2) antinociception induced by endogenous delta-opioid receptor agonists, [Leu5] and [Met5]enkephalin. The antinociception produced by i.c.v. administered beta-endorphin has been attributed to the release of [Met5]enkephalin in the spinal cord and its antagonism by naltriben support the finding that enkephalins interact with delta 2-opioid receptors in the spinal cord to mediate antinociception. beta-Endorphin may be interacting at receptors other than delta 1- or delta 2-opioid receptors in the brain, perhaps the putative epsilon receptors, to mediate their effects because neither i.c.v. administered BNTX nor naltriben inhibited its activity.

Topics: Animals; Benzylidene Compounds; beta-Endorphin; Brain; Enkephalin, Leucine; Enkephalin, Methionine; Injections, Intraventricular; Injections, Spinal; Male; Mice; Naltrexone; Pain; Receptors, Opioid, delta; Spinal Cord

It has been shown previously that opioids induce antinociceptive effects at peripheral sites in the presence of inflammatory processes. Besides being elicited by local injection of opioids, such effects can also be obtained by activation of intrinsic opioid mechanisms, e.g. following stress. In the present study the possible role of cytokines in this mechanism was investigated. Unilateral inflammation of the hindpaw of rats was induced by local injection of Freund's complete adjuvant. Intraplantar injection of tumor necrosis factor alpha (TNF alpha) or interleukin-6 induced a dose-dependent increase in the threshold in the paw pressure test in the inflamed but not in the non-inflamed paw. This increase was prevented by local injection of naloxone and the mu-opioid receptor specific antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) as well as by 3-E7, an universal opioid peptide antibody. In rats pretreated with cyclosporin A to suppress the immune system, the antinociceptive effect of TNF alpha was completely inhibited. In concert with previous studies these data indicate that the tested cytokines release opioid peptides (e.g. beta-endorphin and/or enkephalins) from immune cells of the inflamed tissue which act on opioid receptors present on sensory nerve terminals, resulting in antinociception.

Topics: Amino Acid Sequence; Animals; beta-Endorphin; Cyclosporine; Cytokines; Inflammation; Interleukin-6; Male; Molecular Sequence Data; Narcotic Antagonists; Pain; Peripheral Nervous System; Rats; Rats, Wistar; Receptors, Opioid; Tumor Necrosis Factor-alpha

We examined whether streptozotocin-induced diabetes can modulate beta-endorphin-induced antinociception in mice. While beta-endorphin administered i.c.v. produced a dose-dependent inhibition of the tail-flick response in both diabetic and non-diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The ED50 value of beta-endorphin administered i.c.v. in diabetic mice was significantly lower than that in non-diabetic mice. The antinociceptive effects of beta-endorphin administered i.c.v. in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. beta-Endorphin administered i.t. also produced a dose-dependent antinociception in both diabetic and non-diabetic mice. However, the ED50 value of kappa-opioid receptor antagonist. On the other hand, the antinociceptive potency of DPDPE, a selective delta-opioid agonist, administered i.t. is significantly increased in diabetic mice, as compared with non-diabetic mice, whereas, the antinociceptive potency of U-50,488H, a kappa-opioid receptor agonist, administered i.t. is significantly less than in non-diabetic mice. These results suggest that diabetes may modulate beta-endorphin-induced antinociception differently at the spinal and supraspinal levels.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; beta-Endorphin; Cerebral Ventricles; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Naltrexone; Narcotic Antagonists; Pain; Pyrrolidines; Reference Values

To extend the knowledge on the central effects of cytokines, we studied the effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity in rats. After central administration, both tumor necrosis factor alpha and interleukin-1 alpha significantly (P < 0.001) increase the nociceptive thresholds as measured by the hot-plate test. Tumor necrosis factor alpha, but not interleukin-1 alpha decreases spontaneous locomotor activity evaluated by the Animex test. The increase in nociceptive thresholds induced by tumor necrosis factor alpha or interleukin-1 alpha is not affected by the opiate receptor antagonist naloxone, or antisera against the endogenous opioids beta-endorphin, met-enkephalin or dynorphin. The analgesic effect of tumor necrosis factor alpha is completely antagonized by anti-IL-1 antibodies. Moreover, the cyclooxygenase inhibitor indomethacin does not antagonize the increase of nociceptive thresholds induced by either cytokine.

Topics: Analgesia; Animals; beta-Endorphin; beta-Lipotropin; Cerebral Ventricles; Cross Reactions; Dose-Response Relationship, Drug; Injections, Intraventricular; Interleukin-1; Male; Motor Activity; Pain; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Sensory Thresholds; Tumor Necrosis Factor-alpha

The effects of cholecystokinin octapeptide (CCK8s) given intrathecally (i.t.) on antinociception and the release of immunoreactive Met-enkephalin in the spinal perfusate induced by intraventricular (i.vt.) injection of beta-endorphin were studied in anesthetized rats. beta-Endorphin (5 micrograms) given i.vt. inhibited the tail-flick response. The inhibition of the tail-flick response induced by beta-endorphin was blocked dose-dependently by CCK8s (0.1-7 micrograms) given i.t. The antagonistic effect of CCK8s on beta-endorphin-induced inhibition was blocked dose dependently by co-intrathecal injection of proglumide (3 and 10 micrograms), a CCK8s receptor antagonist. beta-Endorphin (5 micrograms) given i.vt. elicited a release of immunoreactive Met-enkephalin in the spinal perfusate. Repeated injections of the same dose of beta-endorphin released about the same amount of the immunoreactive Met-enkephalin in the spinal perfusate. CCK8s at concentrations from 1 x 10(-9) to 1 x 10(-6) M added into the spinal perfusate decreased the release of Met-enkephalin induced by beta-endorphin given i.vt. in a dose-dependent manner. The results suggest that CCK8s may attenuate beta-endorphin-induced inhibition of the tail-flick response by inhibiting the release of Met-enkephalin from the spinal cord.

Topics: Animals; beta-Endorphin; Depression, Chemical; Enkephalin, Methionine; Injections, Intraventricular; Injections, Spinal; Narcotic Antagonists; Pain; Proglumide; Rats; Rats, Inbred Strains; Reaction Time; Receptors, Opioid; Receptors, Opioid, delta; Reflex; Secretory Rate; Sincalide; Spinal Cord; Tail

Pretreatment (i.c.v.) of mice with L-arginine but not D-arginine potentiated beta-endorphin-induced (i.c.v. administered) inhibition of the tail-flick response. The potentiation was attenuated by N omega-nitro-L-arginine methyl ester, a selective inhibitor of nitric oxide synthase. This observation suggests that increased production of nitric oxide from L-arginine mediates the potentiation of beta-endorphin-induced antinociception.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; beta-Endorphin; Drug Synergism; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Pain

To test the hypothesis that hypertension diminishes pain perception, a study was made that evaluated the relation between arterial blood pressure and thermal pain perception in human subjects. The average mean arterial pressure in all 20 men studied (10 hypertensive, 10 normotensive) proved to be significantly related to both thermal pain threshold (p = 0.05) and tolerance (p = 0.003). The difference between normotensive and hypertensive groups in baseline and posttest plasma levels of beta endorphin was also significant (p = 0.02) and indicated an interaction between endogenous opioids and blood pressure. Other recent studies of hypertension in relation to hypalgesia were also reviewed. An increased pain threshold was found in hypertensive versus normotensive rats. In cats, electrical stimulation of vagal afferent nerves (cardiopulmonary baroreceptors) suppresses nociceptive responses, and both pharmacologic elevation of blood pressure and vascular volume expansion produce antinociception. Together with preliminary findings in human studies, these results indicate an interaction between pain-controlling and cardiovascular regulatory functions that is probably mediated by the baroreceptor system.

Topics: Adult; beta-Endorphin; Blood Pressure; Humans; Hypertension; Male; Nociceptors; Pain; Pain Measurement; Pain Threshold

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; beta-Endorphin; Chromatography, High Pressure Liquid; Chronic Disease; Female; Headache; Homovanillic Acid; Humans; Male; Middle Aged; Migraine Disorders; Muscle Contraction; Pain; Radioimmunoassay; Reference Values

A series of studies with humans as well as experiments carried out on animals could show that physical exercise leads to temporary hypoalgesia. Reduced sensitivity to pain is not only demonstrable after long-distance exercise (such as marathon run) but also after intensive physical exercise on a laboratory ergometer. Pain threshold elevation is most pronounced during maximal exertion, but hypoalgesia remains present also after exercise is stopped demonstrating that a systemic analgetic effect is induced by the exercise process. Pre-exercise pain threshold level is returned to approximately 60 minutes after the exercise. The cause of the exercise-induced hypoalgesia is probably an activation of central pain inhibitory mechanisms by the "stimulus" of physical exercise (stimulation- or stress-induced analgesia). Central pain inhibitory systems are thereby triggered by the stimulation of afferent nerve endings (group III and IV) in the skeletal muscle. The same trigger mechanism also plays a role as a release stimulus for hormones such for beta-endorphin which is increased under physical exercise. Plasma-beta-endorphin is probably not directly involved in the exercise-induced hypoalgesia but is rather a "marker" for the activating of central analgesia mechanisms. Stress-induced hypoalgesia plays also a role in the coronary heart disease. The activation of endogenous analgetic mechanisms leads to a part of the myocardial ischaemia provoked by exercise being silent under exercise. Completely asymptomatic myocardial ischaemia patients display a generalized hypoalgesia which is demonstrable independent of an exertion stimulus and which indicates a central set-point change in the antinociceptive system.

Topics: Adult; Analysis of Variance; beta-Endorphin; Coronary Disease; Double-Blind Method; Epinephrine; Exercise; Exercise Test; Humans; Hydrocortisone; Male; Naloxone; Norepinephrine; Pain; Pain Measurement; Sensory Thresholds

Several studies have described changes in beta-endorphin-like immunoreactivity (beta-ELI) in the rat brain in response to pain and stress stimuli. In order to ascertain the components of beta-ELI, brain samples of rats experiencing acute prolonged (tonic) pain were evaluated for their beta-ELI and later submitted to a chromatographic purification allowing the measurement of beta-endorphin (beta-EP) and acetyl beta-EP. The chromatographic analysis of both ventromedial hypothalamus (VMH) and periaqueductal grey (PAG) homogenates indicates that beta-ELI is distributed in several fractions including shortened forms of beta-EP and their respective acetylated compounds. Quantitatively, while beta-ELI in formalin-injected animals was increased by 48% in VMH and 45% in PAG in respect to controls, the net increase of purified beta-EP was 1100% and 470%, respectively, for VMH and PAG. Moreover, the maximal increase of beta-ELI was evident at 120 min, in both tissues. In contrast, the beta-EP peak was reached at 30 min in VMH and at 60 min in PAG. Acetyl beta-EP was unchanged by treatment in both central areas. No correlation of beta-ELI and beta-EP was found in VMH. These data demonstrate that the evaluation of beta-ELI gives a poor estimate of beta-EP changes, due to several components of the endorphin family.

Topics: Animals; beta-Endorphin; Brain; Chromatography, High Pressure Liquid; Male; Pain; Periaqueductal Gray; Radioimmunoassay; Rats; Rats, Inbred Strains

Our previous studies indicate that endogenous opioids (primarily beta-endorphin) released during stressful stimuli can interact with peripheral opioid receptors to inhibit nociception in inflamed tissue of rats. This study sought to localize opioid precursor mRNAs and opioid peptides deriving therefrom in inflamed tissue, identify opioid containing cells and demonstrate their functional significance in the inhibition of nociception. In rats with Freund's adjuvant-induced unilateral hindpaw inflammation we show that: (i) pro-opiomelanocortin and proenkephalin-mRNAs (but not prodynorphin mRNA) are abundant in cells of inflamed, but absent in non-inflamed tissue; (ii) numerous cells infiltrating the inflamed subcutaneous tissue are stained intensely with beta-endorphin and [Met]enkephalin (but only few scattered cells with dynorphin) antibodies; (iii) beta-endorphin is present in T- and B-lymphocytes, monocytes and macrophages; and (iv) whole-body irradiation suppresses stress-induced antinociception in the inflamed paw. Taken together, these data suggest that endogenous opioid peptides are synthesized and processed within various types of immune cells at the site of inflammation. Immunosuppression abolishes the intrinsic antinociception in inflammatory tissue confirming the functional significance of these cells.

Topics: Analysis of Variance; Animals; beta-Endorphin; Calcitonin Gene-Related Peptide; Endorphins; Freund's Adjuvant; Gene Expression; Hindlimb; Inflammation; Male; Nerve Fibers; Nucleic Acid Hybridization; Oligonucleotide Probes; Pain; Pain Measurement; Rats; Rats, Inbred Strains; RNA, Messenger; T-Lymphocytes; Whole-Body Irradiation

To verify whether plasma beta-endorphin and bradykinin affects the pathophysiology of myocardial ischemia and the perception of cardiac pain, 35 patients with coronary artery disease were subjected to treadmill testing and 48-hour Holter ECG monitoring to measure their pain thresholds. Patients were divided into two groups during exercise testing: group 1 (N = 19) who had ST segment depression, and group 2 (N = 16), who had chest pain. Both groups were then compared with 12 age-matched control subjects. Pain thresholds were measured after Holter ECG monitoring, and blood samples were drawn before and immediately after exercise. No statistical differences were noted between groups 1 and 2 with regard to the severity of myocardial ischemia as assessed by ST segment depression or exercise tolerance time. The frequency of the episodes of silent myocardial ischemia in group 1 was found to be significantly (p less than 0.05) higher than that in group 2. The duration of the episodes of silent myocardial ischemia in group 1 was 41.9 minutes (range 3 to 343 minutes), which was significantly (p less than 0.05) longer than that in group 2 (11.5 minutes; range 0 to 74). The pain threshold in group 1 was a statistically (p less than 0.05) higher value than that in group 2. Although the resting plasma beta-endorphin level in group 1 was not statistically significantly different from values in either group 2 or the control group, during exercise the plasma beta-endorphin levels in both group 1 and the control group were significantly (p less than 0.05) elevated in comparison with their resting levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: beta-Endorphin; Bradykinin; Coronary Disease; Electrocardiography, Ambulatory; Exercise Test; Humans; Male; Middle Aged; Pain; Perception; Risk Factors; Sensory Thresholds

Besides the neurophysiological component of pain, subject of a previous article, biochemical components exist. Humorals, released in case of tissue damage and inflammation, cause among others vasodilatation, increased permeability of the blood vessels, itching and pain. Other endogenous biochemical products, among which endorphin beta, lessen the pain. It is also possible to further diminish the noxious (painful) action of the biochemical products with anti-biochemical medication.

Topics: beta-Endorphin; Capillary Permeability; Humans; Inflammation; Neurotransmitter Agents; Pain

The influence of prolonged pain upon hypothalamic opioid peptide release in vitro was examined in rats subjected to Freund's adjuvant (FA)-induced unilateral inflammation of the hindlimb. Basal release of enkephalin (ENK) but not beta-endorphin (END) or dynorphin (DYN) was increased 10 days following FA treatment. Superfusion of corticotropin-releasing factor (CRF; 10(-8) M) stimulated the release of opioid peptides in control hypothalami. CRF, however, failed to modify beta-END and DYN release in hypothalami of FA-treated rats, whereas ENK release was markedly reduced. In contrast, KCl-stimulated opioid peptide release did not differ between FA and control hypothalami. These data demonstrate that prolonged inflammatory pain alters the responsiveness of hypothalamic opioid systems to CRF. It is suggested that this effect is mediated at the level of the CRF neuron or its receptor.

Topics: Animals; Arthritis, Experimental; Behavior, Animal; beta-Endorphin; Corticotropin-Releasing Hormone; Dynorphins; Electroshock; Endorphins; Enkephalin, Methionine; Hypothalamus; In Vitro Techniques; Inflammation; Male; Pain; Potassium Chloride; Radioimmunoassay; Rats; Rats, Inbred Strains; Restraint, Physical; Stress, Psychological

Topics: Adrenocorticotropic Hormone; Back Pain; beta-Endorphin; Chronic Disease; Electric Stimulation Therapy; Electrodes, Implanted; Humans; Pain; Spinal Cord; Substance P; Time Factors

Tiapride icv 400 micrograms/rabbit exhibited analgesic and synergistic effects on electroacupuncture analgesia (EAA) in rabbits. Both electroacupuncture (EA) and tiapride (icv 400 micrograms/rabbit) enhanced the beta-endorphin-like immunoreactive substance (beta-EPIS) level in cerebrospinal fluid (CSF) measured by radioimmunoassay (RIA). When EA and tiapride were used in combination, a further increase of beta-EPIS content was found. The results suggested that promotion of beta-EPIS release by tiapride may be one of the mechanisms of synergistic effect of tiapride on EAA.

Topics: Acupuncture Analgesia; Animals; beta-Endorphin; Electroacupuncture; Female; Male; Pain; Rabbits; Radioimmunoassay; Sensory Thresholds; Tiapamil Hydrochloride

Previous studies using the technique of microinjection into brain nuclei indicated that the periaqueductal gray (PAG), nucleus accumbens, habenula and amygdala play an essential role in pain modulation and that these nuclei possibly act through a 'mesolimbic neural loop' to exert an analgesic effect, in which Met-enkephalin (MEK) and beta-endorphin (beta-EP) have been implicated as the two major opioid peptides involved in antinociception. In the present study performed in rabbits, intracranial microinjection was supplemented with push-pull perfusion and radioimmunoassay to determine whether the release of enkephalins (ENK) and beta-EP was increased in these nuclei when the putative neural circuit was activated by morphine administered into one of the nuclei. The results showed: (1) microinjection of morphine into the PAG increased the release of ENK and beta-EP in the N. accumbens, and vice versa; (2) microinjection of morphine into the N. accumbens increased the release of ENK and beta-EP in the amygdala, and vice versa; (3) morphine microinjected into the PAG caused an increase in the release of ENK and beta-EP in the amygdala and vice versa, although the release of ENK in PAG was statistically not significant. These results indicate that PAG, N. accumbens and amygdala are connected in a network served by a positive feedback circuitry.

Topics: Amygdala; Animals; beta-Endorphin; Enkephalins; Limbic System; Male; Microinjections; Morphine; Neurons; Nucleus Accumbens; Organ Specificity; Pain; Perfusion; Rabbits

Beta-endorphin/beta-lipotropin immunoreactivity (BE/BLPH-IR) content was evaluated in the CSF of patients suffering by deafferentation pain syndromes. BE/BLPH-IR CSF concentrations of these patients were compared with those obtained in a group of patients affected by low back pain and in a control group without pain problems. No statistically significant variation in BE/BLPH-IR levels were found between controls and subjects with different types of chronic pain.

Topics: Adult; Aged; Back Pain; beta-Endorphin; beta-Lipotropin; Brachial Plexus; Extremities; Female; Humans; Male; Middle Aged; Neuralgia; Pain; Radioimmunoassay; Syndrome

Cholera toxin, an agent that impairs the function of Gs transducer proteins, was injected (0.5 microgram/mouse, icv) and the antinociceptive activity of opioids and clonidine was studied 24h later in the tail-flick test. In these animals, an enhancement of the analgesic potency of morphine, beta-endorphin and clonidine could be observed. Cholera toxin did not modify the antinociception evoked by the enkephalin derivatives DAGO and DADLE. Pertussis toxin that catalyses the ADP ribosylation of alpha subunits of Gi/Go regulatory proteins was given icv (0.5 microgram/mouse). This treatment reduced the analgesic effect of opioids and clonidine. However, while the analgesia elicited by DAGO, DADLE and clonidine was greatly decreased, the effect of morphine and beta-endorphin was reduced to a moderate extent. It is concluded that Gi/Go regulatory proteins functionally coupled to opioid and alpha 2 receptors are implicated in the efficacy displayed by opioids and clonidine to produce supraspinal analgesia. Moreover, these two receptors are susceptible to regulation by a process that might involve a Gs protein.

Topics: Analgesia; Animals; beta-Endorphin; Cerebral Ventricles; Cholera Toxin; Clonidine; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; GTP-Binding Proteins; Injections, Intraventricular; Male; Mice; Morphine; Narcotics; Pain; Pertussis Toxin; Receptors, Adrenergic, alpha; Virulence Factors, Bordetella

alpha N-acetyl human beta-endorphin-(1-31) injected icv to mice antagonized the analgesic activity of beta-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of alpha N-acetyl beta-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of alpha N-acetyl human beta-endorphin-(1-31) was partially retained by the shorter peptide alpha N-acetyl human beta-endorphin-(1-27) and to a lesser extent by beta-endorphin-(1-27), beta-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated beta-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM [125I]-Tyr27 human beta-endorphin-(1-31) specific binding, the first step (20 to 30% of the binding) was abolished with an apparent IC50 of 0.35 nM, and the rest with an IC50 of 200 nM. It is suggested that alpha N-acetyl beta-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins Gi/Go.

Topics: Acetylation; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Mice; Pain; Structure-Activity Relationship; Tail; Time Factors

The involvement of the beta-endorphin (B-EP) system during acute prolonged (tonic) pain was investigated by biochemical and behavioral approaches in freely-moving rats after subcutaneous injection of a small amount of a dilute formaldehyde solution (0.08 ml, 5%) in a forepaw. Beta-endorphin-like immunoreactivity levels were increased over the respective control groups in rats killed 30, 60 and 120 min after injection in discrete regions of the rat brain, namely ventro-medial hypothalamus, ventro-basal thalamus and periaqueductal gray matter, and at 30 and 60 min in postero-medial thalamus. In a separate group of experiments a small amount of anti-B-EP or normal rabbit serum was injected in the lateral ventricle; 6 h later rats received formalin injection as in previous groups and their behavior was scored over the following 2 h. A significant hyperalgesia (as expressed by an increase in the amount of time rats spent licking or chewing the injected paw) was observed 10-50 min and 70-80 min after formalin in the anti-B-EP icv-injected group. Other behavioral parameters such as general motor activity, grooming and limb flexion were not different in the two groups, nor was animal behavior prior to formalin injection. Altogether these data suggest that the central beta-endorphin system is triggered by prolonged noxious stimulation in freely-moving animals, and in turn plays a physiological role in the modulation of the reaction to, or perception of, tonic pain.

Topics: Acute Disease; Animals; Behavior, Animal; beta-Endorphin; Brain; Formaldehyde; Grooming; Male; Motor Activity; Movement; Pain; Periaqueductal Gray; Rats; Rats, Inbred Strains; Thalamus; Ventromedial Hypothalamic Nucleus

Plasma beta-endorphin (beta-END) levels were measured before, after exercise tests and at the onset of spontaneous angina in 23 anginal patients (group 1), 23 patients with silent myocardial ischemia (group 2) and 15 healthy volunteers (group 3). The pain perception in three groups was also measured. Before and after exercise, the concentration of beta-END in group 1 was significantly lower than that in group 2 and group 3. The concentration of beta-END during onset of spontaneous angina was also lower than that of angina-free period in group 1. There was no significant difference of beta-END between group 2 and 3. The values of the pain threshold and tolerance in group 1 were lower than those of group 2 and 3. These data suggested that plasma levels of beta-END may be related to occurrence of angina. The anginal patients had a hypersensitivity and hypotolerance for pain. A positive correlation was found between plasma beta-END and pain threshold, the levels of beta-END might affect the pain perception during the onset of myocardial ischemia.

Topics: Angina Pectoris; beta-Endorphin; Coronary Disease; Exercise Test; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Sensory Thresholds

Topics: 3-Iodobenzylguanidine; Antineoplastic Agents; beta-Endorphin; Child; Child, Preschool; Enkephalin, Methionine; Humans; Iodine Radioisotopes; Iodobenzenes; Neuroblastoma; Pain; Time Factors

Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and 5-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.

Topics: Aged; beta-Endorphin; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Neurotransmitter Agents; Nociceptors; Pain; Pain Measurement; Paresthesia; Parkinson Disease; Sensation; Sensory Thresholds

Exogenous opioids can produce localized opioid receptor-mediated antinociception in peripheral inflamed tissue. Previous studies show that activation of endogenous opioids by a cold water swim in rats with hind paw inflammation results in a similar local antinociceptive effect but suggest that pituitary-adrenal opioid pools are not directly involved in producing this effect. Here we show increased amounts of opioid peptides in immune cells infiltrating the inflamed tissue. Furthermore, we demonstrate immunoreactive opioid receptors on peripheral terminals of sensory neurons. The local administration of antibodies against opioid peptides or receptors or systemic pretreatment with the immunosuppressant cyclosporine blocks cold water swim-induced antinociception. These findings suggest that antinociception in inflammation can be brought about by endogenous opioids from immune cells interacting with opioid receptors on peripheral sensory nerves.

Topics: Animals; Antibodies, Monoclonal; beta-Endorphin; Dynorphins; Enkephalin, Methionine; Freund's Adjuvant; Immunoenzyme Techniques; Inflammation; Male; Neurons, Afferent; Pain; Physical Exertion; Radioimmunoassay; Rats; Rats, Inbred Strains; Receptors, Opioid; Reference Values; Skin

Intravenous injection of beta-endorphin antiserum (AS) with antibody titres of 1:1,600, 1:3,200, 1:12,800, and 1:20,000 decreased the voltage threshold in the tail-shock test (electrocutaneous nociceptive stimulus) in rats for 2 days, after which time control levels were regained. In the case of AS of titres 1:12,800 and 1:20,000 this threshold then increased to above control levels for about 40 and 100 days, respectively. This effect was abolished by naloxone. In the same rats, an injection of AS of titre 1:1,600 did not alter the latency of the tail-flick test (thermal nociceptive stimulus) but AS of titres 1:3,200, 1:12,800, and 1:20,000 decreased it for 1-4 h, the actual length of time being titre-dependent. After control levels had been regained, there was no further change in latency in the tail-flick test in the subsequent 42 days. Injection with preimmune serum did not change either voltage threshold or latency in the two tail-stimulation tests in control rats. Thus the hyperalgesic short-term effect seen in response to treatment with beta-endorphin AS was more pronounced in response to an electrocutaneous stimulus than to a thermal one, and the long-term selective analgesic effect was present in response to rats given electrocutaneous stimulation but not to thermal stimulation. It is proposed that beta-endorphin AS has a two-stage selective effect: a reduction in beta-endorphin release followed by a 'rebound' increase.

Topics: Animals; Antibodies; beta-Endorphin; Electroshock; Hot Temperature; Male; Naloxone; Nociceptors; Pain; Rats; Rats, Inbred Strains

The hypothesis that blood-borne beta-endorphin modulates nociception was examined with corticotropin-releasing factor (CRF) as a potent and selective agent to stimulate its release from the pituitary gland. Intravenously administered CRF produced a dose-related antinociception in rats as determined by measuring paw-lick latencies on a 50 degrees C hot plate. A dose of 25 nmol/kg of CRF was comparable in both magnitude and duration of antinociception to a 7,500 nmol/kg (= 2.5 mg/kg) dose of morphine sulfate. The antinociceptive effect of CRF was blocked by both hypophysectomy and dexamethasone pretreatment, suggesting that it was mediated by hormone release from the anterior pituitary corticotrophs. Furthermore, the effect of CRF was antagonized by 1) naltrexone, 2) naltrexone methyl bromide, and 3) passive immunization with anti-beta-endorphin antiserum. Together, these data support the hypothesis that opiate-active, beta-endorphin, released by pituitary corticotrophs, participates in the physiological modulation of nociception in rats.

Topics: Analgesics; Animals; beta-Endorphin; Corticotropin-Releasing Hormone; Dexamethasone; Male; Morphine; Naltrexone; Pain; Pituitary Gland; Radioimmunoassay; Rats; Rats, Inbred Strains; Reference Values; Time Factors

Topics: Arthritis, Rheumatoid; beta-Endorphin; Dermatitis; Humans; Immunity, Innate; Interleukin 1 Receptor Antagonist Protein; Killer Cells, Natural; Pain; Sialoglycoproteins; Stress, Physiological; Superoxide Dismutase

The level of an endogenous opioid (peak B endorphin) was measured in chromatographically fractionated cerebrospinal fluid (CSF) sampled from two groups of chronic pain patients before and after intrathecal saline (placebo) injection. As assessed by a verbal rating scale, one group reported no change in their level of pain (non-responders, NR; n = 6) while the other group reported complete or greater than 50% pain relief (placebo responders, PR; n = 14). We find, as has been reported previously, that initial peak B levels were lower (by 50%) in these chronic pain patients' CSF than in CSF from pain-free (PF) normal controls (P less than 0.001, t-test). Peak B levels measured from CSF of the NR group undergoing this procedure did not change (P greater than 0.4, paired t-test). In contrast, a significant 2.3-fold increase was measured in the CSF peak B level of the PR group (P less than 0.05, paired t-test). This is the first direct evidence that a CSF opioid is correlated with placebo pain relief in chronic pain patients. Peak B is a potent analgesic substance when administered by the intracerebroventricular route in mice and its level is related to the patients' pain status in a presumably causal manner.

Topics: beta-Endorphin; Chronic Disease; Humans; Injections, Intraventricular; Pain; Placebos

In 38 women with uncomplicated vaginal delivery at term, the different pain intensities during spontaneous labor were correlated to the plasma beta-endorphin and cortisol concentrations simultaneously examined. The pain intensities subjectively assessed were numerically categorized. The women in labor categorized to pain intensities 0 to III were in comparable stages of cervical dilatation. The hormone concentrations were measured by means of radioimmunoassay. The lowest hormone levels were found after abolition of pains of labor by epidural anesthesia: beta-endorphin 42 pg/ml, cortisol 318 ng/ml (mean values). The hormone concentrations rose progressively with increasing intensities of labor pain. The highest concentrations were observed in the first few minutes after delivery i.e. immediately after cessation of the extreme pains of expulsive labor: beta-endorphin 118 pg/ml, cortisol 449 ng/ml. Statistically significant, positive correlations were calculated between beta-endorphin and cortisol concentrations in plasma and the self-reported pain intensities (p less than 0.001 and p less than 0.01 resp.). Thus, highly elevated beta-endorphin levels in plasma do not abolish pain, probably they modulate it. Within the first four hours postpartum the concentrations of the two stress-stimulated hormones dropped rapidly. The endorphin level fell from 118 pg/ml immediately after delivery to 38 pg/ml in the above mentioned period, the cortisol level from 449 ng/ml to 302 ng/ml. One to three days after delivery the beta-endorphin and cortisol concentrations in maternal plasma were largely normalized, this means they then approximately corresponded to the values being found in nonpregnant women under normal conditions.

Topics: Adrenal Cortex; Adult; beta-Endorphin; Female; Humans; Hydrocortisone; Labor, Obstetric; Male; Pain; Postpartum Period; Pregnancy; Radioimmunoassay; Regression Analysis

Thirty-six women in their second or third pregnancies were studied in two groups (control and exercise) to determine whether plasma alpha-endorphin levels could be elevated by exercise conditioning during pregnancy. Aerobic training was performed on a bicycle ergometer. Both groups were monitored throughout pregnancy by frequent gynecologic examinations. During labor, both groups of women had pain perception assessment. Blood was sampled for levels of beta-endorphin, cortisol, human growth hormone, and prolactin. Plasma beta-endorphin was found elevated compared to controls in patients who exercised throughout pregnancy. This difference was maintained throughout labor and pain perception during labor was reduced in the patients who exercised. Cortisol, human growth hormone, and prolactin levels were lowered during labor for the exercise-conditioned patients. Exercise conditioning during pregnancy seems to be beneficial in reducing pain perception during labor (as determined by measurement of visual analog pain scales) and in reducing stress levels during labor.

Topics: Arm; beta-Endorphin; Female; Hormones; Humans; Ischemia; Labor, Obstetric; Pain; Pain Measurement; Physical Exertion; Pregnancy; Self Concept; Sensory Thresholds

In rats beta-endorphin antiserum systemic injection decreased during 1-2 days the threshold of tail-shock and latency of tail-flick tests, and during subsequent 85 days increased the threshold of tail shock, but not changed the latency of tail-flick tests. Naloxone injection blocked the increasing of thresholds, but not changed the latency of tail tests. It is suggested that antiserum evokes the first inhibition and the second selective activation of endogenous antinociceptive opioid system with affinity to electric nociception.

Topics: Animals; beta-Endorphin; Electric Stimulation; Hot Temperature; Immune Sera; Naloxone; Pain; Rats; Reaction Time; Sensory Thresholds; Time Factors

The aim of the present paper is to verify in an experimental pharmacological animal model the role played by beta-endorphin in the modulation of the response to pain inducer by electrical dental pulp stimulation.

Topics: Animals; beta-Endorphin; Dental Pulp; Electric Stimulation; Pain; Rabbits

Brain and blood iron deficiency (ID) can be nutritionally induced. Significant behavioral and brain-biochemical changes are observed in rats rendered iron deficient, including complete reversal of the circadian cycles of motor activity, changes in thermoregulation and stereotyped behavior, and an increased pain threshold. The increase in pain threshold is affected by diurnal factors and peripheral treatment with beta-endorphin has a significant analgesic effect, implicating selective changes in the blood-brain barrier. These effects along with modifications in responses to dopaminergic drugs, interactions of ID with neuroleptic drugs, and modifications in behavior as a result of selective brain lesions, lead to two conclusions: this animal model is appropriate for human anemia and the best explanation for the variety of behavioral and brain biochemical changes in ID rats is that the principal effect of brain ID is a selective decrease in the functional level of the dopaminergic D2 system.

Topics: Amphetamine; Anemia, Hypochromic; Animals; Antipsychotic Agents; Apomorphine; beta-Endorphin; Body Temperature Regulation; Brain; Disease Models, Animal; Dopamine; Iron; Iron Deficiencies; Learning; Motor Activity; Pain; Rats; Receptors, Dopamine; Sensory Thresholds

Thirteen patients with pain from various causes were treated by electroacupuncture for 30 min. Cerebrospinal fluid (CSF) was obtained before and after treatment. Opioid-like substances in the CSF were fractionated by high pressure liquid chromatography and assayed by competitive receptor binding using a mu-specific radioligand, [D-ala2, MePhe4, gly-ol5]-enkephalin (DAGO). Opioid activity, associated with a fraction, eluted at 18-20% acetonitrile, consistently showed an increase in level after acupuncture. Two other fractions eluted at larger concentrations of acetonitrile also increased significantly after acupuncture; however the increase was not consistently observed in every patient. Measurements of beta-endorphin and dynorphin by radioimmunoassay indicated that 80 and 60% of the patients, respectively, had a higher level of these peptides after acupuncture. The nature of the opioid activity, eluted at 18-20% acetonitrile is unknown; however a small amount of it could be found in various parts of the brain of rat.

Topics: beta-Endorphin; Chromatography, High Pressure Liquid; Chronic Disease; Dynorphins; Electroacupuncture; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Humans; Pain; Pain Management; Radioimmunoassay

Intravenous infusion of lidocaine has a pain-relieving effect in patients with painful diabetic neuropathy. We measured plasma beta-endorphin (beta-EP), dynorphin immunoreactivity (DYN), and met-enkephalin (MET) before and after lidocaine infusion in 8 patients with painful diabetic neuropathy and in 10 controls. The pretreatment level of beta-EP and DYN was identical in the two groups. After lidocaine, beta-EP increased in diabetic patients from 3.4 to 5.5 pmol/L (median) (p less than 0.02) and in controls from 3.4 to 5.0 pmol/L (p less than 0.02). The concentration of DYN was stable, and MET was undetectable before and after lidocaine. Lidocaine reduced symptoms and pain score in diabetic patients was uncorrelated with the changes in beta-EP. Intravenous lidocaine increased plasma beta-EP and diminished complaints in patients with painful diabetic neuropathy.

Topics: Adult; beta-Endorphin; Diabetic Neuropathies; Dynorphins; Endorphins; Female; Humans; Lidocaine; Male; Middle Aged; Pain; Radioimmunoassay

The effect of the endogenous opioid peptides, methionine-enkephalin (Met-ENK), beta-endorphin (beta-END) and dynorphin-(1-17) (DYN) on the aversive behavior produced by intrathecal (i.t.) administration of substance P (SP) was studied in mice. A low dose of i.t. administered Met-ENK gave a marked reduction of the SP-induced response. In the tail-flick assay, such doses of Met-ENK were ineffective in producing antinociception. At much higher doses, however, Met-ENK obtained antinociceptive activity. In contrast, beta-END and DYN had about the same potency in inhibiting the SP-induced behavioural response and in the tail-flick test, respectively. These results suggest that opioid peptides, particularly enkephalin neurons in the spinal cord influence SP-induced aversive behaviour.

Topics: Animals; beta-Endorphin; Dose-Response Relationship, Drug; Dynorphins; Enkephalin, Methionine; Injections, Spinal; Mice; Nociceptors; Pain; Reaction Time; Substance P

The purpose of this study was to assess the biochemical mechanisms underlying spinal cord stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation. Basal cerebrospinal fluid beta-endorphin levels were below the normal range. No significant change of norepinephrine, epinephrine, dopamine, beta-endorphin, beta-lipotropin, or adrenocorticotropic hormone levels were found after SCS. A 50% increase of cerebrospinal beta-endorphin and beta-lipotropin levels occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the derangement of the endogenous opioid system in chronic pain conditions and suggest that the beta-endorphin response to SCS could have clinical value in predicting the success of treatment.

Topics: Adult; Aged; Aged, 80 and over; beta-Endorphin; beta-Lipotropin; Chronic Disease; Electric Stimulation Therapy; Endorphins; Female; Humans; Male; Middle Aged; Neurotransmitter Agents; Pain; Pain Management; Spinal Cord; Statistics as Topic

Normal or pregnant rats were treated orally for 21 days or throughout pregnancy with water or increasing doses of morphine and killed on days 7, 14, and 21 of pregnancy and 1 day post partum. At these time intervals, plasma, pituitary, and hypothalamic concentrations of beta-endorphin and methionine enkephalin were measured in normal and pregnant rats. Moreover, pituitary and hypothalamic concentrations of the two peptides were also measured in fetuses and newborn. Plasma beta-endorphin and methionine enkephalin increased significantly during pregnancy without any specific effect of morphine. Pituitary concentrations of beta-endorphin were not modified either by pregnancy or morphine treatment, while methionine enkephalin concentrations increased on days 7 and 11 of pregnancy, in both water- and morphine-treated rats. The pattern of the two peptides in the hypothalamus is completely superimposable to the one present in the pituitary with the exception of an increase of beta-endorphin on day 21 of pregnancy, which is more evident in control animals. Consistently with our observations in human newborn and the neurological dysfunctions we observed in them, the concentrations of both the peptides are significantly increased in the hypothalamus of fetuses and newborn of morphine-treated mothers, while in the pituitary only beta-endorphin concentrations are increased.

Topics: Animals; Animals, Newborn; beta-Endorphin; Brain; Enkephalin, Methionine; Female; Fetus; Hypothalamus; Morphine; Pain; Pituitary Gland; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains

beta-Endorphin-like immunoreactivity (B-EP-LI) levels have been investigated in the ventral periaqueductal gray matter (vPAG) of rats killed 30, 60 or 120 min after the subcutaneous injection of dilute formalin (0.08 ml, 5%) in one fore- or hindpaw, or comparable handling. B-EP-LI was estimated by radioimmunoassay, using an anti-camel B-EP serum directed against the C-terminal portion of B-EP molecule. In both fore- and hindlimb groups vPAG B-EP-LI values were significantly increased 60 and 120 min after the injection relative to controls. Values from animals killed 120 min after formalin injection were higher than the ones at 30 and 60 min, forelimb effects being quantitatively more pronounced. The increase in B-EP-LI appeared distributed along the whole rostrocaudal extent of the region.

Topics: Animals; beta-Endorphin; Formaldehyde; Male; Pain; Periaqueductal Gray; Rats; Rats, Inbred Strains; Time Factors

Mice subjected to defeat in a social conflict paradigm display an analgesic response that is apparently mediated by endogenous opioids. It is blocked by naloxone and shows full cross-tolerance to and from morphine. The present study investigated the contribution of sources of endogenous opioids outside of the central nervous system, namely the pituitary and adrenal glands. Treatment known to enhance (metyrapone pretreatment), reduce (2% saline in the drinking water) or block (dexamethasone pretreatment) the release of beta-endorphin from the anterior pituitary did not affect the display of analgesia in defeated mice. Similarly, treatments known to enhance (reserpine pretreatment) or block release of enkephalins (removal of the adrenals or hexamethonium pretreatment) from the adrenal medulla also failed to influence defeat-induced analgesia in the expected manner. If anything, adrenalectomy enhanced and reserpine pretreatment suppressed the analgesic response to defeat. The data are discussed in terms of providing evidence that defeat-induced analgesia is mediated primarily by endogenous opioids released and acting within the central nervous system.

Topics: Animals; beta-Endorphin; Central Nervous System; Dexamethasone; Endorphins; Enkephalins; Male; Mice; Pain; Pituitary-Adrenal System; Reserpine; Social Behavior; Stress, Psychological

Plasma and CSF levels of beta-Endorphin (beta-End) were measured by radioimmunoassay in three groups of human subjects. The first group consisted of healthy adults, and only plasma beta-End was determined. The second group consisted of patients showing non-painful neurological diseases. The third group consisted of patients suffering from acute pain due to herniated intervertebral discs. In the last two groups, beta-End levels were measured in plasma and CSF. The results showed that plasma levels of beta-End were similar in the first two groups of patients. In contrast, patients with acute pain showed significantly increased levels of beta-End in plasma. CSF levels of beta-End did not show significant differences among the groups. The results suggest that the increase in plasma levels of beta-End was a consequence of the stress produced by acute pain.

Topics: beta-Endorphin; Humans; Intervertebral Disc Displacement; Pain; Radioimmunoassay; Stress, Physiological

Morphine administered concurrently by i.c.v. plus intrathecal (i.t.) injection produces a multiplicative (synergistic) interaction for antinociception in the tail-flick test. Inasmuch as i.c.v. administered beta-endorphin has been proposed to produce antinociception by activating a descending pain inhibitory system different from that activated by morphine, the present experiments compared the two systems in mice. The responses to i.c.v., i.t. and combinations of i.c.v. plus i.t. administration of morphine and beta-endorphin were evaluated by determination of ED50 values which were plotted as isobolograms and compared to calculated theoretical additive ED50 values. The following combinations gave additive interactions: i.c.v. plus i.t. beta-endorphin, i.c.v. beta-endorphin plus i.t. morphine and i.t. morphine plus i.t. beta-endorphin. These results were consistent with the hypothesis that i.c.v. beta-endorphin stimulates supraspinal epsilon receptors which activate a descending pathway involving enkephalinergic neuronal mediation and spinal postsynaptic mu receptors. Stimulation of these mu receptors by i.t. morphine or i.t. beta-endorphin together with the supraspinal effect of beta-endorphin resulted in an additive interaction. Multiplicative interactions were obtained for the following combinations: i.c.v. morphine plus i.t. morphine, i.c.v. morphine plus i.t. beta-endorphin and i.c.v. morphine plus i.c.v. beta-endorphin. Morphine administered i.c.v. stimulated supraspinal mu receptors to activate a descending pain inhibitory pathway which is mediated spinally by monoamines. The i.t. agonists in this case activated the spinal mu receptor which is presumed to be part of the beta-endorphin descending pathway described above. Thus, when both pathways were activated simultaneously the interaction was multiplicative.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesia; Animals; beta-Endorphin; Drug Tolerance; Efferent Pathways; Injections, Intraventricular; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Morphine; Naltrexone; Pain; Spinal Cord

Topics: Adolescent; Adult; beta-Endorphin; Female; Heroin Dependence; Humans; Male; Pain; Sensory Thresholds; Substance Withdrawal Syndrome

Spinal administration of low doses of dynorphin, beta-endorphin or Met-enkephalin produces a potent, dose-dependent increase in the nociceptive threshold in the unanesthetized frog, Rana pipiens. Nociceptive thresholds were determined by using the acetic acid test, previously shown to be a sensitive indicator of antinociception in this amphibian species. Of particular interest, spinally administered dynorphin produces a potent antinociception in frogs without any signs of motor dysfunction seen after spinally administered dynorphin in mammalian species.

Topics: Analgesics; Animals; beta-Endorphin; Dynorphins; Endorphins; Enkephalin, Methionine; Pain; Rana pipiens; Sensory Thresholds; Spinal Cord

Male rats were injected s.c. once daily during the first week of life with beta-endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail-flick latencies of the groups on day 9 correlated well with hot-plate and tail-flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides.

Topics: Animals; Animals, Newborn; beta-Endorphin; Endorphins; Female; Hot Temperature; Hyperesthesia; MSH Release-Inhibiting Hormone; Nervous System; Nociceptors; Pain; Psychomotor Performance; Rats

In children with burn injuries we found, in earlier studies, an inverse association of plasma beta-endorphin immunoactivity (iB-EP) and pain levels. To further explore the effects of burn trauma on the peripheral release of beta-endorphin and the occurrence of centrally mediated stress analgesia, plasma iB-EP levels and tail flick latency (TFL) were measured in rats subjected (while anesthetized) to scald injury. In comparison to sham burn (dip in tepid water), burn injury increased plasma iB-EP and TFL; both the duration and magnitude of these effects were directly proportional to the extent of burns. In rats receiving no treatment, TFLs were unchanged throughout the time of the burn experiments. At 2 days post-burn TFLs were invariably back to pre-burn levels. Administration of the long-acting opioid antagonist naltrexone prior to burn injury prevented the rise in TFL. Thus the trauma of burns appeared to bring about a stress-induced analgesia (SIA). The marked increase in iB-EP during this SIA and its antagonism by naltrexone suggest that it was opioid and hormonal in character.

Topics: Analgesia; Animals; beta-Endorphin; Burns; Endorphins; Male; Pain; Rats; Rats, Inbred Strains; Stress, Physiological

Capsaicin, a neurotoxic agent that induces a decrease in hypothalamic beta-endorphin, a specific antiserum and human beta-endorphin fragment 6 31, a peptidergic beta-endorphin antagonist have been used in the attempt of selectively affecting the function of beta-endorphinergic system and of evaluating the possible role of this peptide in the analgesic effect of morphine. All 3 experimental approaches resulted in a decrease of the analgesia induced by morphine, thus suggesting that beta-endorphin is involved in the effect of morphine.

Topics: Animals; beta-Endorphin; Brain; Capsaicin; Endorphins; Injections, Intraventricular; Male; Morphine; Pain; Peptide Fragments; Rats; Rats, Inbred Strains; Sensory Thresholds

The effect of soman poisoning on the levels of methionine enkephalin and beta-endorphin in mice and rats were determined. Soman poisoning produced no significant effect on methionine enkephalin levels in the striatum of rats or mice or beta-endorphin levels in the pituitary gland of mice. In rats beta-endorphin levels were significantly reduced 24 hr post soman poisoning, but returned to control levels by 48 hr. In vitro, the hydrolysis of leucine enkephalin by aminopeptidase was virtually complete by 30 min and found to be the major route of degradation. The release of TYR-GLY-GLY in the presence or absence of puromycin (10 microM) was found to be low (less than or equal to 2.0%). A minor effect on TYR release in the presence of GLY-GLY-PHE-MET (50 microM) was insignificant. Preincubation of mouse striatum homogenates with soman (1 or 10 microM) did not inhibit the hydrolysis of leucine enkephalin. These results suggest that the long term antinociception following soman exposure is not due to either altered concentration of endogenous opioid-like substances or inhibition of the enzymes responsible for their degradation.

Topics: Animals; beta-Endorphin; Corpus Striatum; Endopeptidases; Endorphins; Enkephalin, Leucine; Male; Mice; Neprilysin; Pain; Pituitary Gland; Rats; Rats, Inbred Strains; Soman

The relationship among therapeutically induced affective arousal, depressive symptoms, pain and beta-endorphin levels were explored on 6 patients with chronic, active rheumatoid arthritis. An ABA, n of 1 study methodology was utilized, replicated 5 times. This procedure allowed the analysis of individualized changes across time in response to the therapeutic regimen. The results indicated that the treatment regimen activated the beta-endorphin system, particularly during the early and late phases of treatment. However, beta-endorphin response had little effect on reports of subjective pain. Depressive symptoms were affected positively by the treatment but were not strongly correlated to the beta-endorphin response. The results suggest that pain and depression represent independent systems and that beta-endorphin levels serve more as stress markers than analgesics in chronic, organic pain.

Topics: Adult; Aged; Arthritis, Rheumatoid; beta-Endorphin; Defense Mechanisms; Depression; Endorphins; Female; Gestalt Therapy; Humans; Middle Aged; Neurotic Disorders; Pain; Pain Management; Psychotherapy

We studied 27 patients who complained of pain, for which no organic basis could be found, and 11 patients without pain. All patients were depressed according to clinical diagnosis and Beck Depression Inventory (BDI) scores. Plasma beta-endorphin levels were found not to differ between the two groups or across other variables. The patients who complained of pain had significantly higher scores on the BDI.

Topics: Adolescent; Adult; Aged; beta-Endorphin; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Pain; Sensory Thresholds

The contribution of stress-induced and opioid-dependent mechanisms to the modulation of experimental pain was studied in man under different conditions. The contribution of these mechanisms to the possible attenuation of acute cardiac pain in human patients was also studied. According to the present series of investigations, stress-induced mechanisms might be involved in the modulation of pain caused by physical exercise but not by concurrent subacute pain or transcutaneous nerve stimulation. The lack of any negative correlation between the pain intensity and the release of stress hormones indicates that stress mechanisms do not attenuate acute ischaemic pain of the cardiac origin. The use of an opioid-antagonist, naloxone, and the measurement of plasma levels of beta-endorphin did not reveal any contribution of endogenous opinoids to pain modulation in the current study.

Topics: beta-Endorphin; Coronary Disease; Endorphins; Humans; Naloxone; Neurosecretory Systems; Pain; Physical Exertion; Stress, Physiological; Stress, Psychological; Transcutaneous Electric Nerve Stimulation

During pregnancy, rats and humans show an increase in pain threshold that is mediated by an endorphin system. In order to determine whether plasma beta-endorphin and/or other factors of pituitary origin are involved in pregnancy-induced analgesia in the rat, the effects of hypophysectomy (day 12 of pregnancy) or pharmacological suppression of pituitary function via dexamethasone administration (day 14-21 of pregnancy) were investigated. Hypophysectomy did not affect either the magnitude of the increase or the pattern of change in pain threshold despite the resulting decrease in stress-induced plasma beta-endorphin concentrations. However, the observed effect of the surgical and/or postsurgical procedure on pain threshold confounded unequivocal interpretation of these results. Pharmacological suppression of pituitary function with dexamethasone (2 micrograms/ml), a non-invasive procedure, also produced a significant decrease in resting plasma beta-endorphin levels. As was observed for surgical removal of the pituitary gland, this treatment did not produce a significant alteration in the magnitude of the increase in jump threshold. Furthermore, no correlation was found between plasma beta-endorphin concentrations and jump threshold values on day 21 of pregnancy. These results indicate that the pituitary gland does not play an essential role in the maintenance of opioid analgesia during pregnancy. It is suggested that pregnancy-induced analgesia depends on central rather than peripheral opioid systems.

Topics: Animals; beta-Endorphin; Dexamethasone; Female; Hypophysectomy; Pain; Pain Measurement; Pituitary Gland; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains; Stress, Physiological

The sensitivity to painful and sexual stimuli in male rats was markedly suppressed immediately after ejaculation and enhanced after the postejaculatory refractory period. The suppression of pain sensitivity induced by sexual activity was reversed, but sexual behavior was only slightly affected by intraperitoneal (i.p.) injection of the opioid antagonist naloxone (5 mg). Plasma concentrations of beta-endorphin-like immunoreactivity were unaffected by sexual activity. Injection of beta-endorphin (10 micrograms s.c.) markedly raised plasma concentrations of beta-endorphin-like immunoreactivity within 1 min of injection but did not affect the sensitivity to painful stimulation or the display of sexual behavior. It is suggested that while ejaculation may activate opioid receptor mechanisms, which affect the sensitivity to painful, but not sexual, stimuli, elevation of beta-endorphin in the blood does not affect the sensitivity to either sexual or painful stimuli in male rats.

Topics: Animals; beta-Endorphin; Male; Naloxone; Nociceptors; Pain; Rats; Rats, Inbred Strains; Sexual Behavior, Animal

An improved radio-immunoassay using an antiserum directed towards the N-terminal part of the endogenous opioid peptide beta-endorphin 1-31 (beta-EP) was validated and applied to a study of beta-EP in plasma during ischaemic pain. Experimental ischaemic pain induced in seven healthy volunteers by the submaximal effort tourniquet test did not change plasma beta-EP or adrenocorticotrophin. Plasma beta-EP was determined in 21 patients with acute myocardial infarction (AMI) and in seven patients with unstable angina pectoris. Plasma beta-EP was 4.9 fmol/ml with 95% confidence limits, 3.2-7.8 fmol/ml in AMI patients at admittance, and 2.9 (2.0-3.4) fmol/ml one week later in stable and pain-free condition (p less than 0.05). The level in 49 healthy persons was 2.8 (2.4-2.9) fmol/ml. Elevated beta-EP levels were found in five AMI patients with cardiogenic shock and in four AMI patients dying within 24 h after admittance compared to the rest of AMI patients (p less than 0.02). beta-EP was not elevated during unstable angina pectoris, although pain scores were similar to AMI. The AMI group revealed a significant, although weak, positive correlation between plasma beta-EP and pain score (Spearman r = 0.49, p less than 0.05), while there was no correlation during unstable angina pectoris. beta-EP was not correlated to the amount of morphine required within the 48 h after admittance of AMI patients. We conclude that the increase of beta-EP in plasma during AMI may be due to stressful factors other than ischaemic pain and that it is questionable whether beta-EP in plasma is related to antinociception.

Topics: Adult; Aged; Angina Pectoris; beta-Endorphin; Blood Specimen Collection; Female; Humans; Male; Middle Aged; Muscles; Myocardial Infarction; Pain; Physical Exertion; Radioimmunoassay; Tourniquets

Intradermal inoculation of rats at the tail base with Mycobacterium butyricum led to the gradual development of an arthritic swelling of the limbs which peaked at 3 weeks and subsided thereafter. Arthritic rats displayed a loss of body weight, hypophagia, and hypodipsia in addition to a disruption of the diurnal rhythms of ingestive behavior and of core temperature. The activity of adenohypophyseal beta-endorphin-(beta-EP) secreting corticotrophs, in contrast to prolactin-(PRL) secreting lactotrophs, was increased in arthritic rats. Indeed, hypertrophy of the adrenal glands was seen. Arthritic rats also showed an elevation in spinal cord levels of immunoreactive dynorphin (DYN), an endogenous ligand of the kappa-opioid receptor. The paws and tail of arthritic rats showed lower thresholds in response to noxious pressure (hyperalgesia), higher thresholds in response to noxious heat (hypoalgesia), and no change in their response to noxious electrical stimulation. Neither naloxone nor ICI-154, 129 (a preferential delta-receptor antagonist) modified the responses of the paw or tail to pressure. However, MR 2266 (an antagonist with higher activity at kappa-receptors) decreased thresholds to pressure in arthritic, but not control, rats; that is, it potentiated the hyperalgesia. This action was stereospecific. None of the antagonists modified the response to heat. MR 2266 did not affect the response to pressure in rats with acute inflammation produced by yeast. Thus, the potentiation of pressure hyperalgesia by MR 2266 in chronic arthritic rats is highly selective. Arthritic rats showed a reduced response to the analgesic effect of a kappa-agonist (U-50,488H), whereas the response to a mu-agonist (morphine) was enhanced. These effects were specific to nociception in that their influence upon endocrine secretion (PRL and beta-EP) was otherwise changed. The secretion of beta-EP and PRL was stimulated by both morphine and U-50,488H, and the influence of U-50,488H upon the release of beta-EP (from the adenohypophysis) was enhanced in arthritic rats. It is suggested that polyarthritis is a complex condition entailing many changes, both behavioral and endocrinological. Further, arthritic rats cannot simply be described as "hyperalgesic": of critical importance is the nature of the nociceptive stimulus applied. The parallel alterations in spinal cord pools of DYN and kappa-receptors (see also Millan et al., 1986) and the changes in the influence on nociception of kappa-

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arthritis, Experimental; beta-Endorphin; Body Temperature; Body Weight; Endorphins; Feeding Behavior; Male; Morphine; Narcotic Antagonists; Pain; Prolactin; Pyrrolidines; Rats; Receptors, Opioid

Spontaneously elevated nociceptive threshold levels were markedly diminished after Naloxone injections in 4 patients with congenital insensitivity to pain. This finding suggested the hypothesis of a relation between congenital insensitivity to pain and permanent hyperfunction of an endomorphinic system. Radio-immunoassay of CSF beta-endorphin was performed in all 4 cases. The normal or only slightly elevated levels cannot explain electrophysiologic findings, but as a function of the multiplicity of endogenous opioid systems, hyperactivity of another endomorphinic system cannot be excluded. Other hypotheses may also be proposed.

Topics: beta-Endorphin; Endorphins; Humans; Naloxone; Pain; Pain Insensitivity, Congenital; Radioimmunoassay; Sensory Thresholds

Chronic arthritic pain was induced by intradermally inoculating rats at the tail-base with Mycobacterium butyricum, which results in swelling, inflammation, and hyperalgesia of the joints. These symptoms peak at 3 weeks after inoculation and disappear by 10 weeks. The following changes were seen at 3 weeks. Immunoreactive dynorphin (ir-Dyn) and ir-alpha-neo-endorphin (alpha-NE) manifested comparable patterns of change. Their levels were increased in the anterior, but not neurointermediate, pituitary. The thalamus showed a rise in ir-Dyn and ir-alpha-NE, but no alterations were seen in other brain regions. In each case, cervical, thoracic, and lumbosacral sections of the spinal cord showed a rise in ir-Dyn and ir-alpha-NE: This was most pronounced in the lumbosacral region, where the magnitude of these shifts correlated with the intensity of arthritic symptoms. In addition, a moderate elevation in ir-methionine-enkephalin (ME) was seen in lumbosacral spinal cord. In brain, ir was not changed. The level of ir-beta-endorphin (beta-EP) was elevated both in the plasma and the anterior, but not the neurointermediate, pituitary. In addition, the content of messenger RNA encoding the beta-EP precursor, proopiomelanocortin (POMC), was enhanced in the anterior lobe. Thus, there was a selective activation of synthesis of beta-EP in, and its secretion from, the anterior lobe. In no brain tissue did levels of ir-beta-EP change. At 10 weeks postinoculation, the above changes were no longer apparent, indicating their reversibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arthritis; Arthritis, Experimental; beta-Endorphin; Brain; Brain Chemistry; Chronic Disease; Diprenorphine; Disease Models, Animal; Dynorphins; Endorphins; Hypothalamus; Male; Mesencephalon; Pain; Rats; Rats, Inbred Strains; Receptors, Opioid; Spinal Cord; Thalamus

Topics: Acupuncture Therapy; Animals; beta-Endorphin; Dynorphins; Electric Stimulation Therapy; Endorphins; Enkephalins; Naloxone; Naltrexone; Pain; Rats; Sensory Thresholds; Transcutaneous Electric Nerve Stimulation

This study was undertaken to determine the association, if any, of plasma endorphins with pelvic pain in a defined population. The study group was comprised of 37 patients who presented to the emergency room at Wishard Memorial Hospital for evaluation of gynecologic complaints. These subjects were divided into 3 groups depending on the degree of pelvic pain assessed both by the subject and the examining physician. Group I (control) consisted of those subjects who were pain-free (9 subjects). Group II contained those whose pelvic pain was not felt to require hospital admission (18 subjects). Group III subjects represented those with pelvic pain whose diagnosis warranted hospitalization (10 subjects). Plasma endorphin levels were determined on each subject before and after pelvic examination using standard radioimmunoassay techniques. Data analysis was accomplished by analysis of variance methods. The timing of the pelvic examination made no difference on the plasma endorphin levels. Levels between groups were statistically similar, though differences between both group I and group II, and that of group III levels approached significance.

Topics: Abdomen; Adolescent; Adult; beta-Endorphin; Endorphins; Female; Genital Diseases, Female; Humans; Pain; Pelvis; Pregnancy; Radioimmunoassay

Eleven male and 15 female sheep were subjected to electroacupuncture (EA) treatment, using 2 needle loci described in the Chinese veterinary literature as Yao Pang (lumbar region) and San Yang Lu (1 thoracic limb). Noninjurious cutaneous stimuli were applied, using a calibrated pin-prick probe, a clamp, and a contact heat (75 to 95 C) probe. Cutaneous pain thresholds (PT) were quantified in 7 body areas during control (no acupuncture needles and no electrostimulation) and EA experiments, before and after IV injection of naloxone. Using each animal as its own control, each EA experiment was classified as inducing either good or poor anagelsia on the basis of whole-body PT values. Plasma concentrations of immunoreactive beta-endorphin (beta E) and prolactin were quantified in sequential plasma samples collected at 9-minute intervals throughout all experiments. Electroacupuncture at each locus increased (P less than 0.01) PT (ie, caused cutaneous analgesia) in 6 of 7 body areas, and increased (P less than 0.05) plasma concentrations of immunoreactive beta E and prolactin. In EA experiments in which good analgesia was induced, plasma beta E was increased more (P less than 0.05) than in EA experiments in which poor analgesia was induced. This difference was more evident for the Yao Pang locus. Generally, plasma prolactin concentrations were increased more with good analgesia than with poor analgesia for the Yao Pang locus. Electroacupuncture stimulation of the San Yang Lu locus was associated with higher plasma beta E concentrations than that associated with the Yao Pang locus. Increases in plasma prolactin concentrations were comparable between loci.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acupuncture Therapy; Analgesia; Animals; beta-Endorphin; Electric Stimulation; Endorphins; Female; Male; Naloxone; Orchiectomy; Ovariectomy; Pain; Pain Management; Prolactin; Sensory Thresholds; Sheep

Serum beta-endorphin was assayed without knowledge of study subject category in 44 consecutive patients with primary fibromyalgia syndrome, 3 patients with rheumatoid arthritis (RA), and 30 normal controls, all females. Mean serum beta-endorphin levels were 81 +/- 28 pg/ml in patients with fibromyalgia, whereas those in normal controls and patients with RA were 73 +/- 17 pg/mg and 73 +/- 18 pg/ml, respectively. These differences were not statistically significant. Serum beta-endorphin levels did not correlate with relevant clinical variables in either fibromyalgia or RA groups.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; beta-Endorphin; Circadian Rhythm; Endorphins; Female; Humans; Middle Aged; Pain; Rheumatic Diseases; Seasons; Syndrome

Topics: Analgesics; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Drug Tolerance; Electric Stimulation; Endorphins; Hypothalamus; Morphine; Pain; Rats; Sensory Thresholds

We investigated 8 healthy male volunteers, evaluating RII and RIII thresholds every 6 h starting from noon, for a 24-h period. Both reflex responses exhibited a circadian rhythmicity: the lowest values were found in the early morning (9.1 +/- 3.0 and 13.1 +/- 4.4 mA, respectively), while the highest values were observed at midnight (13.1 +/- 3.5 and 18.5 +/- 5.3 mA). Also mean cosinor analysis indicated the existence of a significant rhythm with acrophase at 20:12 for RII and 22:29 for RIII. In 4 subjects, beta-endorphin plasma (beta-EP) level was tested during the day. No correlation was observed between circadian changes of beta-EP and RIII threshold. Other factors are likely to be involved in the circadian variation of nociceptive flexion reflex in man.

Topics: Adult; beta-Endorphin; Circadian Rhythm; Endorphins; Humans; Male; Muscle Contraction; Muscles; Nociceptors; Pain; Reaction Time; Reflex; Sensory Thresholds; Sural Nerve; Touch

The reason for the absence of pain perception in silent myocardial ischemia is unknown. A role of increased endorphinic activity in patients with silent ischemia has been postulated. To further investigate this hypothesis, 10 men with documented coronary artery disease and previous positive electrocardiographic findings during exercise without anginal pain were studied. Six healthy volunteers served as control subjects. The protocol included 2 bicycle exercise tests, the first test serving as baseline and the second performed after administration of naloxone, a specific opiate antagonist. Plasma beta-endorphin levels were measured by radioimmunoassay in both tests at rest, at peak exercise level and after recovery. All patients underwent thallium-201 scintigraphy after coronary vasodilation to provide an additional independent marker of ischemia. All patients showed stress-induced reversible perfusion abnormalities. No patient reported pain after naloxone application. Exercise duration, blood pressure and heart rate were not significantly altered by naloxone. Plasma beta-endorphin levels ranged from 18 +/- 6 pg/100 microliters (mean +/- standard deviation) at rest to 22 +/- 6 pg/100 microliters during exercise in the patient group and from 20 +/- 5 to 27 +/- 9 pg/100 microliters in the control subjects. Thus, there was no significant increase of plasma beta-endorphins during exercise or after naloxone administration, nor was there any difference observed between patients and control group. These data support the view that endorphinic activity does not play an essential role in the pathophysiology of silent myocardial ischemia.

Topics: beta-Endorphin; Blood Pressure; Electrocardiography; Endorphins; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Naloxone; Pain

When rats were tested more than two weeks following surgery, lesions of the medial basal hypothalamus centered on the arcuate nucleus enhanced a form of foot-shock stress-induced analgesia (SIA) that was not blocked by injections of the opiate receptor blocker, naltrexone (6 mg/kg;). These arcuate nucleus lesions reduced the SIA produced by the same stressor when similar rats were tested 3-4 days following surgery. Finally, when similar rats were tested more than 2 weeks following surgery these lesions reduced a different form of SIA that was blocked by naltrexone. There were no effects of the lesions or naltrexone on baseline pain reactivity in any of the experiments. We suggest that arcuate nucleus lesions disrupt a system important for the elaboration of opiate-mediated SIA (Expt. 4), perhaps by damaging the brain's beta-endorphin system. In response to damage to this opioid analgesic system, we hypothesize that the damaged brain initiates time-dependent compensatory changes in an undamaged non-opioid analgesic system, resulting in enhanced non-opiate-mediated SIA.

Topics: Analgesia; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Biotin; Body Weight; Drinking Behavior; Electroshock; Endorphins; Feeding Behavior; Male; Naltrexone; Pain; Rats; Rats, Inbred Strains; Stereotaxic Techniques; Stress, Psychological; Wheat Germ Agglutinins

Growing evidence indicates that most patients with coronary artery disease frequently have episodes of painless myocardial ischemia. Previous studies from our institution show that the severity and duration of myocardial ischemia are necessary but not sufficient factors to explain the occurrence of anginal pain. The responses to a battery of painful stimuli were studied in 12 patients with predominantly painless (group A) and in 15 patients with predominantly painful (group B) ischemic episodes. The severity of myocardial ischemia as assessed by the measurement of ST-segment depression during exercise stress testing and during ambulatory electrocardiographic monitoring was comparable in the 2 groups. Patients in group A had a significantly higher threshold and tolerance for forearm ischemia (+32%, p less than 0.05; +120%, p less than 0.001), cold (+100%, p less than 0.05; +180%, p less than 0.01) and electrical skin stimulation (+145%, p less than 0.01; +109%, p less than 0.01), but the overlap between the 2 groups was often appreciable. In the 6 patients with the longest tolerance times for forearm ischemic pain (all in group A) and in the 5 having the shortest tolerance times (all in group B), plasma levels of beta endorphin, met-enkephalin, noradrenaline and adrenaline were similar during both the basal state and the induction of forearm ischemic pain. Thus, a generalized defective perception of painful stimuli plays an important role in many patients with predominantly painless myocardial ischemia. Other mechanisms, however, may also be important, particularly in patients whose threshold and tolerance values overlap with those of patients who have predominantly painful myocardial ischemia.

Topics: Angina Pectoris; beta-Endorphin; Chronic Disease; Coronary Disease; Endorphins; Enkephalin, Methionine; Humans; Male; Middle Aged; Norepinephrine; Pain; Perception; Sensory Thresholds

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxytryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator of pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) greater than that induced by L-5HTP alone. Neither the subjective pain threshold and tolerance nor the RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.

Topics: Adult; beta-Endorphin; Carbidopa; Drug Therapy, Combination; Endorphins; Humans; Migraine Disorders; Pain; Sensory Thresholds; Tryptophan

Plasma, pituitary, and hypothalamic levels of the endogenous opioid peptide beta-endorphin were measured by radioimmunoassay and column chromatography in female rats 8 wk after the induction of diabetes with streptozocin (STZ) and in control female rats. In addition, pain perception was determined by measuring the latency to paw lick or jump after being placed on a hot plate. Plasma levels of immunoreactive beta-endorphin (IR-BE) were significantly reduced in STZ-induced diabetic female rats, as were the content and concentration of IR-BE in the neurointermediate lobe of the pituitary (NIL) and the content of IR-BE in the hypothalamus. The concentration but not the content of IR-BE in the anterior pituitary (AP) of the STZ-induced diabetic rats was increased significantly. Streptozocin-induced diabetes also resulted in a significant reduction in the total protein content of the AP, NIL, and hypothalamus. Column chromatography indicated that the decrease in IR-BE in the plasma, NIL, and hypothalamus represented a decrease in beta-endorphin, whereas the increase in IR-BE in the AP represented an increase in both beta-endorphin and beta-lipotropin. Diabetic animals consistently showed decreased latencies to paw lick or jump when subjected to hot-plate testing after 7 wk. These findings suggest that in female rats, central and peripheral endogenous opiate levels and tolerance to nociceptive thermal stimulation were diminished by 8 wk of chemically induced diabetes.

Topics: Animals; beta-Endorphin; Diabetes Mellitus, Experimental; Endorphins; Female; Hypothalamus; Male; Pain; Pain Measurement; Pituitary Gland; Pituitary Gland, Anterior; Rats; Rats, Inbred Strains

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.

Topics: 5-Hydroxytryptophan; Adult; beta-Endorphin; Carbidopa; Drug Therapy, Combination; Endorphins; Humans; Migraine Disorders; Pain; Sensory Thresholds

A series of experiments examined the hypothesis that mating produced analgesia in the Syrian hamster can be blocked by opiate antagonists. The first experiment established a dose response relation to painful footshock. Females were more responsive to footshock than males (p less than 0.001). The second experiment demonstrated that ten minutes of mating reduced responsiveness of both males and females to a moderate intensity of footshock. The third experiment replicated the effect of mating on the responsiveness of males to footshock, but did not demonstrate any effect of the opiate antagonist naltrexone on mating induced analgesia. The fourth experiment demonstrated that limited mating stimulation (five intromissions) has little effect on the responsiveness of sexually inexperienced males to footshock. The fifth experiment replicated the fourth experiment using sexually experienced males and obtained comparable results. Apparently mating induced analgesia in male hamsters is not blocked by opiate antagonists and which raises questions about biological activity of reported changes in endorphin activity during mating.

Topics: Animals; beta-Endorphin; Copulation; Cricetinae; Electroshock; Endorphins; Female; Male; Mesocricetus; Naltrexone; Pain; Reaction Time; Sex Characteristics

Topics: Adrenocorticotropic Hormone; Animals; Baclofen; Behavior, Animal; beta-Endorphin; Brain; Diazepam; Endorphins; gamma-Aminobutyric Acid; In Vitro Techniques; Injections, Intraventricular; Naloxone; Pain; Pituitary Gland; Rats; Receptors, GABA-A; Receptors, Opioid; Seizures; Zinc

The endogenous opioid peptides are derived from three large precursors. Pro-opiocortin and proenkephalin yield [Met]enkephalin, carboxy-extended [Met]enkephalins and [Leu]enkephalin. The fragments of prodynorphin are all carboxy-extended [Leu]enkephalins. Three approaches are of importance for an analysis of the physiological functions of the different endogenous opioid peptides. First, since these peptides interact with more than one of the mu-, delta- and kappa-binding sites and thus with their receptors, it is necessary to synthesize peptides or non-peptides, which bind to only one of the sites. As far as narcotic analgesics are concerned, morphine fulfils these conditions since it interacts almost exclusively with the mu-receptor. Secondly, antagonists are required that are selective for only one of the opioid receptors, even when used in high concentrations. Finally, it is important to find circumscribed areas in the nervous system that possess only one type of opioid receptor. It is now known that in the rabbit cerebellum the opioid receptors are almost exclusively of the mu-type whereas in the guinea-pig cerebellum they are almost exclusively of the kappa-type.

Topics: Animals; beta-Endorphin; Brain; Endorphins; Enkephalins; Guinea Pigs; In Vitro Techniques; Pain; Peptide Fragments; Protein Precursors; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

We evaluated the development of naloxone-reversible and naloxone-non-reversible analgesia induced by footshock in rats of different ages and correlated it with the concentrations of beta-endorphin and dynorphin in brain areas and the spinal cord. We observed that naloxone-non-reversible shock-induced analgesia appeared first and its appearance might be related to the early presence of high dynorphin concentrations in the spinal cord. Naloxone-reversible analgesia appeared later together with the reaching of adult concentrations of cerebral beta-endorphin.

Topics: Analgesia; Animals; beta-Endorphin; Central Nervous System; Dynorphins; Electroshock; Endorphins; Enkephalin, Methionine; Male; Naloxone; Pain; Rats; Rats, Inbred Strains

The analgesic activity of the prototypic opioid peptides for the mu (D-Ala2-Me-Phen4-Gly-ol5-enkephalin [DAGO]) kappa (Dynorphin 1-13), delta (D-Ala2-D-Leu5-enkephalin [DADLE]), or epsilon (beta-endorphin) receptor was assessed in a rat tooth pulp stimulation procedure. All opioid peptides tested and the opioid alkaloid U50, 488H (kappa receptor agonist) significantly elevated response thresholds. The rank order of potency based on the Minimum Effective Dose values was beta-endorphin greater than DAGO = dynorphin A (1-13) amide greater than DADLE greater than dynorphin A (1-13) greater than U50,488H. Based on absolute magnitude, the rank order of dose response slopes was DAGO greater than U50,488H greater than dynorphin A (1-13) amide greater than beta-endorphin greater than DADLE. Dynorphin A (1-13) produced the shallowest dose response slope and the magnitude of response threshold was the lowest for all compounds tested. Finally, the general conclusion that mu agonists are effective against noxious stimuli derived from thermal, chemical, and mechanical is extended by our data to include electrical sources derived from tooth pulp stimulation; kappa agonists are effective against noxious stimuli derived from chemical, mechanical, and electrical sources (tooth pulp stimulation) and delta agonists are effective analgesics against thermal, chemical and electrical stimuli (tooth pulp stimulation).

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; beta-Endorphin; Dental Pulp; Dynorphins; Electric Stimulation; Endorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Pain; Peptide Fragments; Pyrrolidines; Rats; Rats, Inbred Strains

The need for better analgesia during burn dressing changes (BDCs) in acutely burned children led us to assess pain during BDC with a large 0-10 thermometer-like scale which was well accepted and appeared to reflect the varying degrees of pain that patients experienced. Pain scores were obtained at least once each minute throughout 33 BDCs in 15 patients of 8-17 years. Plasma levels of beta-endorphin immunoactivity (iB-EP) were measured at 5 intervals before and after BDC; mean values (+/- S.E.M.) ranged from 30.5 +/- 4.63 pg/ml (before BDC and analgesic) to 19.2 +/- 3.02 pg/ml (immediately following BDC). The mean pain score (MPS) for each BDC was inversely related to the iB-EP levels of that day (P less than 0.001 with 4 of the 5 iB-EP determinations). The MPS varied directly with the extent of burn injury and inversely with weight; the 2 variables together predicted MPS as well as the iB-EP alone (r2 = 43 and 36% respectively).

Topics: Administration, Topical; Adolescent; Analgesics; Bandages; beta-Endorphin; Burns; Child; Debridement; Endorphins; Humans; Pain; Silver Nitrate

Effects of electroacupuncture (EA) on pain threshold and beta-endorphin (beta-End) contents in plasma, pituitary (Pit), hypothalamus (Hyp) and cerebrospinal fluid (CSF) were studied in nontreated, dexamethasone (Dex) treated and adrenalectomized (Adrex) male SD rats by the use of specific determination of rat beta-End (combination of HPLC and RIA). EA increased pain threshold and plasma beta-End with no effect on beta-End contents in Pit, Hyp and CSF. Dex did not affect control pain threshold, but tended to reduce EA-induced increase in pain threshold (EA-analgesia, EAA) and EA-induced increase in plasma beta-End. Adrex increased plasma beta-End without change in control pain threshold. Adrex tended to reduce EAA, but a tendency of further increase in plasma beta-End was observed after addition of EA. Adrex increased Pit beta-End, but no further change in Pit beta-End was observed after addition of EA. A positive correlation between plasma beta-End and plasma ACTH was observed in nontreated, Dex treated and Adrex rats. No correlation between plasma beta-End and potency of EAA was observed in nontreated, Dex treated and Adrex rats. The hind-paw pressure test without EA increased plasma beta-End to the same degree as that produced by EA, and it produced no analgesia. These results suggest that Pit beta-End may not be mainly involved in the development of EAA.

Topics: Acupuncture Therapy; Adrenalectomy; Analgesia; Animals; beta-Endorphin; Dexamethasone; Endorphins; Hypothalamus; Male; Pain; Pituitary Gland; Rats; Rats, Inbred Strains

Endogenous opioid peptides rose to prominence with the discovery of the enkephalins in 1975. Since then, a vast amount of research has been directed toward understanding their role in normal and pathophysiological situations. Although the place of endogenous opioids in psychiatry remains uncertain, there is good evidence that a variety of tumors may secrete endorphins or enkephalins, and these may contribute to the non-metastatic complications of malignant disease. In addition, changes in cerebrospinal fluid met-enkephalin and beta-endorphin after acupuncture may be involved in the effectiveness of this therapy in the treatment of heroin withdrawal and severe pain. The hormonal effects of opiate agonists and antagonists are now well characterized; exercise-induced changes in circulating catecholamines are markedly enhanced by the opiate antagonist naloxone. It is possible that the opiate inhibition of catecholamine release during exercise is a reflection of endogenous opioid modulation of effort perception.

Topics: Acupuncture Therapy; Adrenocorticotropic Hormone; beta-Endorphin; Catecholamines; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalin, Methionine; Growth Hormone; Humans; Luteinizing Hormone; Naloxone; Pain; Physical Exertion; Receptors, Opioid; Sensory Thresholds; Stress, Physiological

The potent opioid peptide beta-endorphin is found in the brain and pituitary with two related fragments, beta-endorphin-(1-27) and beta-endorphin-(1-26). The fragments retain substantial opioid-receptor binding activity but are virtually inactive analgesically. beta-Endorphin-(1-27) inhibits beta-endorphin-induced and etorphine-induced analgesia when coinjected intracerebroventricularly into mice. Antagonism by competition at the same site(s) is suggested from parallel shifts of the dose-response curves of etorphine or beta-endorphin in the presence of beta-endorphin-(1-27). Its potency is 4-5 times greater than that of the opiate antagonist naloxone. beta-Endorphin-(1-26) does not antagonize the antinociceptive action of etorphine or beta-endorphin in doses up to 500 pmol per animal.

Topics: Animals; beta-Endorphin; Binding, Competitive; Dose-Response Relationship, Drug; Endorphins; Etorphine; Male; Mice; Morphinans; Naloxone; Pain; Peptide Fragments; Receptors, Opioid

In order to investigate the involvement of pituitary beta-endorphin in electroacupuncture analgesia (EAA), the effects of hypophysectomy, dexamethasone (Dex) and adrenalectomy on the analgesia and the increase in plasma corticosterone (Cort) and ACTH levels produced by electroacupuncture (EA) were studied in male SD rats. In saline-treated and Dex-treated rats, plasma Cort levels were correlated with plasma ACTH levels. In non-treated rats, the time course of EA-induced increase in pain threshold was similar to that of EA-induced elevation of plasma Cort levels. In the hypophysectomized rats, EAA was significantly reduced and the EA-induced increase in plasma Cort was also abolished. Single administration of a large dose of Dex tended to reduce EAA and significantly reduced the EA-induced increase in plasma Cort and ACTH. Further suppression of pituitary functions by 4 days-treatment with Dex resulted in further reduction of EAA and the EA-induced increase in plasma Cort and ACTH. On the other hand, hind-paw pressure test without EA produced an increase in plasma Cort and ACTH to the same extent as that produced by EA and produced no analgesia. In the adrenalectomized rats, EAA was reduced, and the plasma ACTH level, which was sixteen times higher than that of nonoperated rats, was further elevated 2-fold higher by EA. No correlation between plasma ACTH levels and the increase in pain thresholds was observed in individual rats of the saline-treated and Dex-treated groups. Control pain thresholds were not influenced by hypophysectomy, Dex or adrenalectomy. These results suggest that pituitary beta-endorphin may not be mainly involved in EAA.

Topics: Acupuncture Therapy; Adrenalectomy; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Corticosterone; Endorphins; Hypophysectomy; Male; Pain; Pain Management; Pituitary Gland; Pituitary-Adrenal System; Rats; Rats, Inbred Strains; Sensory Thresholds

We investigated the psychoneuroendocrine and emotional correlates of the natural stress situation of human labor. State anxiety, subjective pain, plasma ACTH, peripheral plasma beta-lipotropin (Beta-LPH), beta-endorphin (Beta-EP), and met-enkephalin (Met-Enk) were serially evaluated at six predetermined time points before, and after labor in a sample of 14 women with normal pregnancies. State anxiety and subjective pain showed a progressive increase during labor, with a levelling during the final stage. Plasma Beta-EP and ACTH showed a similar progressive increasing from baseline until the end of labor. Beta-LPH showed no significant modification. Met-Enk remained at nearly baseline values throughout labor, with a marked progressive rise in the postpartum stage. The findings of this study seem to confirm the role of plasma Beta-EP as a stress hormone. Possible relationship between pain and anxiety curves and plasma Beta-EP are discussed in light of psychobiological studies on stress, the opioid system and analgesia. Plasma Met-Enk, according to our findings, should probably not be regarded as a stress hormone. Its rise in the postpartum stage might be as one of the psychoneuroendocrine mechanisms maintaining elevated prolactin levels during lactation.

Topics: Adrenocorticotropic Hormone; Adult; Anxiety; beta-Endorphin; beta-Lipotropin; Endorphins; Enkephalin, Methionine; Female; Humans; Labor, Obstetric; Pain; Pregnancy; Stress, Physiological

Topics: Adult; Animals; beta-Endorphin; Brain; Brain Chemistry; Cerebrospinal Fluid; Chronic Disease; Electric Stimulation Therapy; Endorphins; Humans; Middle Aged; Pain; Pituitary Gland; Rabbits; Spinal Diseases; Time Factors; Transcutaneous Electric Nerve Stimulation

Plasma levels of the endogenous opioid peptides beta-endorphin and [Met]enkephalin were estimated in 10 osteoarthritic patients during treatment with a sustained-release indomethacin preparation (Osmosin). Significant diurnal variation of beta-endorphin levels was evident both on and off treatment (p less than 0.05, respectively), but the therapy was nevertheless accompanied by decreased morning levels of this peptide; no such changes were recorded for [Met)enkephalin. Whilst the treatment was associated with a reduction of pain, particularly in the evening (p less than 0.02), no correlation was evident between pain and beta-endorphin levels, nor between the patients' perception of pain relief and changes in beta-endorphin levels. The results suggest either that prostaglandins may be involved in the synthesis/release of beta-endorphin, or that the alleviation of stress may in turn reduce the need for continued beta-endorphin production in these patients.

Topics: Aged; Anti-Inflammatory Agents; beta-Endorphin; Delayed-Action Preparations; Endorphins; Enkephalin, Methionine; Female; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Pain

Endorphins and beta-lipotropin have been implicated as the modulators of pain during the labor process. To investigate their possible role during parturition, the present study was undertaken to determine the levels of beta-endorphin, beta-endorphinlike immunoactivity, and beta-lipotropin during labor and delivery. Fourteen patients were evaluated at 4 cm dilatation, complete dilatation, at the time of delivery, and immediately postpartum. In addition, samples were obtained from nine nonpregnant control subjects. The venous levels of beta-endorphinlike immunoactivity and beta-lipotropin were determined, and the beta-endorphin level was calculated. The maternal cerebrospinal fluid (CSF) levels and the newborn umbilical venous level also were determined in the delivery room. A gradual rise was noted in the beta-endorphin, beta-lipotropin, and beta-endorphinlike immunoactivity values up to the time of delivery. There was noted to be a modest decrease in their levels in the immediate postpartum period. These levels were significantly elevated over control samples for both beta-endorphinlike immunoactivity and beta-lipotropin (P less than .05). Values for beta-endorphin were not significantly different from control levels. In addition, maternal CSF levels were found to show modest elevations above the simultaneously drawn venous specimens. The umbilical cord venous samples drawn at delivery were also higher than the simultaneous maternal venous levels. These values, although elevated over control values, were not statistically different from simultaneously drawn maternal venous levels.

Topics: beta-Endorphin; beta-Lipotropin; Endorphins; Female; Fetal Blood; Humans; Labor Stage, First; Labor, Obstetric; Pain; Postpartum Period; Pregnancy

Self-reported levels of pain, anxiety, and depression, and plasma levels of beta-endorphin, epinephrine, norepinephrine, dopamine, and serotonin were measured in 19 arthritic pain patients before and after hypnosis designed to produce pain reduction. Correlations were found between levels of pain, anxiety, and depression. Anxiety and depression were negatively related to plasma norepinephrine levels. Dopamine levels were positively correlated with both depression and epinephrine levels and negatively correlated with levels of serotonin. Serotonin levels were positively correlated with levels of beta-endorphin and negatively correlated to epinephrine. Following hypnotherapy, there were clinically and statistically significant decreases in pain, anxiety, and depression and increases in beta-endorphin-like immunoreactive material.

Topics: Adult; Aged; Anxiety; Arthritis; beta-Endorphin; Catecholamines; Depression; Dopamine; Endorphins; Epinephrine; Female; Humans; Hypnosis; Male; Middle Aged; Norepinephrine; Pain; Pain Management; Personality Inventory; Serotonin

Plasma concentrations of [met]enkephalin (ME) and beta-endorphin (beta E) were measured in samples obtained immediately before and after physiotherapeutic exercises for patients with ankylosing spondylitis (AS), osteoarthritis (OA), or knee injuries. Correlations were sought between opioid peptide concentrations or changes therein, and nature, severity and duration of disease, age, severity of pain reported and pain threshold. No correlation was found with any of the pain parameters. However, there was a possible relationship between age or duration of disease and changes in ME concentrations.

Topics: Adult; Aged; Arthritis; beta-Endorphin; Chronic Disease; Endorphins; Enkephalin, Methionine; Exercise Therapy; Female; Humans; Male; Middle Aged; Pain; Pain Management

The effects of neuroactive peptides on the release of 5-HT were studied. The 5-HT released from the spinal cord was significantly increased by somatostatin, substance P and peripheral pain stimulation (tail pinch), but not affected by neurotensin, beta-endorphin and met-enkephalin. The somatostatin-evoked 5-HT release was inhibited by baclofen and met-enkephalin in vivo but not in vitro. The substance P-evoked 5-HT release was strongly inhibited by baclofen, and slightly potentiated by met-enkephalin in vivo but not in vitro. The tail pinch-induced 5-HT release was inhibited by met-enkephalin and baclofen, but potentiated by naloxone. These findings provide further evidence on the important role of neuropeptides and suggest that the descending serotonergic neurones are modulated by neuropeptide interneurones in the spinal cord.

Topics: Animals; Baclofen; beta-Endorphin; Endorphins; Enkephalin, Methionine; Male; Naloxone; Neuropeptides; Neurotensin; Pain; Rats; Rats, Inbred Strains; Secretory Rate; Serotonin; Somatostatin; Spinal Cord; Substance P

The skin pain threshold was elevated significantly by weak and nonstressful acupuncture stimulation. Although an analgesic effect was obtained by acupuncture stimulation, the beta-E, ACTH, GH and TSH levels were not changed. These findings indicate that these hormone levels were not necessarily related to the skin pain threshold elevation. It is concluded therefore that an analgesic effect was induced without involving the pituitary gland by the weak acupuncture stimulation employed in our study. However, the magnitude of the stimulation may determine whether or not an analgesic effect is mediated by the pituitary gland. The possibility remains that strong acupuncture stimulation produces stress-induced analgesia (SIA). Further detailed research should be attempted.

Topics: Acupuncture Therapy; Adrenocorticotropic Hormone; Adult; Anesthesia; beta-Endorphin; Endorphins; Female; Growth Hormone; Humans; Male; Pain; Pituitary Hormones, Anterior; Sensory Thresholds; Thyrotropin

Electrical stimulation of the periaqueductal gray of the rat's midbrain analgesia leads to an increase in the number of artificial pulmonary metastases from the Walker 256 tumor. In an effort to investigate the influence of the pain suppression system and its associated peptides on this phenomenon, we activated the pain suppression system directly from the Nucleus of the Raphe Magnus, a non-opioid subsystem. After inducing analgesia by direct injection of beta-endorphin on the Nucleus of the Raphe Magnus, we noted an increase in the number of artificial pulmonary metastases. This result could be blocked by pretreatment with naloxone. If the Nucleus of the Raphe Magnus was activated by electrical stimulation sufficient to induce analgesia, the metastatic effect was still present but markedly attenuated.

Topics: Animals; beta-Endorphin; Brain Stem; Carcinoma 256, Walker; Endorphins; Female; Lung Neoplasms; Neoplasm Metastasis; Neoplasms, Experimental; Pain; Periaqueductal Gray; Raphe Nuclei; Rats; Rats, Inbred Strains

We randomly assigned 42 subjects for treatment with transcutaneous electrical nerve stimulation (TENS) to one of three groups: conventional TENS--80 Hz; low frequency TENS--2 Hz; and a control group--TENS without batteries. Pain threshold measurements and blood beta-endorphin levels were obtained at regular intervals before, during, and for 17 hours after TENS application. We found no significant difference in blood beta-endorphin levels between the groups before, during, or immediately after TENS application. The differences in pain threshold and beta-endorphin levels appeared to be a function of the patient-selection process and not the application of TENS. The results indicated that TENS, with the stimulation characteristics used in this study, did not significantly change the measured plasma levels of beta-endorphin. The blind administration of naloxone hydrochloride, an opiate antagonist, did not significantly alter the perceived experimental pain of these subjects. We could find no evidence that TENS altered experimental pain threshold or plasma beta-endorphin levels.

Topics: Analysis of Variance; beta-Endorphin; Electric Stimulation; Electric Stimulation Therapy; Endorphins; Female; Humans; Male; Naloxone; Pain; Pain Management; Radioimmunoassay; Random Allocation; Time Factors; Transcutaneous Electric Nerve Stimulation

The twitch procedure in horses attenuates the increase in the heart rate evoked by pain-inducing stimuli and the reaction of the animals to such stimuli. Endorphin systems are probably involved in the effectiveness of the twitch, since its action is blocked by naloxone and its application increases plasma concentrations of immunoreactive beta-endorphin. The mode of action of the twitch cannot be explained by the generally accepted theory of divertive pain and may resemble that of classical acupuncture.

Topics: Acupuncture Therapy; Animals; beta-Endorphin; Endorphins; Female; Heart Rate; Horses; Male; Naloxone; Pain; Physical Stimulation

Blood was drawn from 14 normal volunteers twice before, immediately after a 1-minute immersion of the nondominant hand in ice water (cold pressor test), and twice during recovery. Serum levels of beta-endorphin, cortisol, prolactin, growth hormone, and opioid activity were determined, and measures of subjective pain appraisal and coping styles were obtained. Cortisol was the only variable to show a significant increase as a function of noxious stimulation. Correlational analysis yielded relationships between neuroendocrine variables and subjective pain appraisal as well as coping styles, suggesting complex interactions between neuroendocrine and psychological processes in human pain.

Topics: Adult; beta-Endorphin; Cold Temperature; Endorphins; Female; Growth Hormone; Hormones; Humans; Hydrocortisone; Male; Pain; Prolactin; Stress, Physiological; Time Factors

Beta-Endorphin was measured by radioimmunoassay in peripheral plasma of nonpregnant women (58 +/- 2.4 pg/ml, n = 17, mean +/- SE), during the first trimester (47 +/- 2.4 pg/ml, n = 11), the second trimester (33 +/- 1.9, n = 11), and the third trimester (49 +/- 2.7 pg/ml, n = 10) of pregnancy, during early (202 +/- 32 pg/ml, n = 12) and advanced labor (389 +/- 78 pg/ml, n = 10), and 30 to 60 minutes post partum (177 +/- 22 pg/ml, n = 12). Mean plasma levels of beta-endorphin were significantly lower in each trimester of gestation than the levels in nonpregnant control subjects. During labor and the early postpartum period, maternal plasma levels of beta-endorphin were significantly elevated. Furthermore, peripheral plasma levels of beta-endorphin during labor fell from 189 +/- 31 to 97.6 +/- 12 pg/ml (n = 13, p = 0.015) in response to epidural anesthesia, as compared to peripheral plasma concentrations of beta-endorphin of 223 +/- 71 and 193 +/- 47 pg/ml prior to and after injection of saline solution into epidural catheters, respectively, in 10 control subjects. Mean plasma levels of beta-endorphin in patients immediately prior to elective repeat cesarean section who were not in labor (151 +/- 23 pg/ml, n = 15) were significantly higher (p less than 0.005) than the levels in third-trimester control subjects. These data indicate that the pain associated with labor and the psychological stress of anticipating an operation are potent stimuli for the pituitary release of beta-endorphin.

Topics: Anesthesia, Epidural; Anesthesia, Obstetrical; beta-Endorphin; Cesarean Section; Endorphins; Female; Humans; Labor, Obstetric; Pain; Pituitary Gland; Postpartum Period; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Stress, Psychological; Time Factors

During pregnancy, rats show a progressive increase in jump threshold which is followed by a precipitous decrease after delivery. Overall, this pattern of change in pain threshold was not affected by adrenalectomy, with or without corticosterone replacement. It appears, therefore, that the adrenal glands are not necessary for the manifestation of opioid analgesia during pregnancy.

Topics: Adrenalectomy; Animals; beta-Endorphin; Corticosterone; Endorphins; Female; Pain; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains; Sensory Thresholds; Stress, Physiological

Rats made nutritionally iron-deficient (ID) have been shown to have a lower brain non-haem. A selective diminution of the binding capacity of the D2-dopaminergic receptors alone was found among nutritionally iron-deficient rats. Peripherally administered beta-endorphin significantly elevated the pain threshold only in the iron-deficient rats. Naloxone blocked the beta-endorphin effect in ID rats. Morphine, as well as haloperidol, elevated the pain threshold in both the iron-deficient and the control rats but significantly more in the former group. No additive effects of combined treatment with beta-endorphin and haloperidol on pain threshold were found. Other neuroleptics also elevated the pain threshold. A possible hypothesis is that dopamine (via beta-endorphin) may play a role in modifying the pain threshold.

Topics: Animals; beta-Endorphin; Blood-Brain Barrier; Circadian Rhythm; Dopamine; Endorphins; Haloperidol; Iron Deficiencies; Male; Morphine; Pain; Rats; Receptors, Dopamine; Sensory Thresholds

Plasma concentration of beta-endorphin was observed during labor in 16 women and correlated with pain assessed subjectively using pain scores. Ten women did not receive any medication during the follow-up. A concomitant increase in pain score and plasma beta-endorphin level was found with advancing labor. In the remaining six women, epidural anesthesia was used to relieve pain. During epidural anesthesia, plasma beta-endorphin levels and pain scores decreased concomitantly. The same effect was found after a repeated dose of the anesthetic. These findings showed a correlation between pain and the secretion of beta-endorphin during labor, but the mode of action of beta-endorphin remains unsolved.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; beta-Endorphin; Endorphins; Female; Humans; Labor, Obstetric; Pain; Pregnancy

Three analogs of human beta-endorphin (beta h-ER) were synthesized by the solid-phase method: [Gln8,Trp27]-beta h-EP (I), [Gln8,Arg9,Trp27]-beta h-EP (II), and [Gln9,Arg11,Trp27]-beta h-EP (III). Radioreceptor binding assay with use of tritiated beta h-EP as primary ligand gave relative potencies as follows: beta h-EP, 100;I, 778;II, 467;III, 449. Relative potencies in an analgesic assay were: beta h-EP, 100;I, 114;II, 165;III, 83. The 8-11 segment of beta h-EP can tolerate a net increase in charge of +2 without diminishing analgesic potency. The substitution of Glu8 may be one of the more dependable means of designing beta-endorphin antagonists.

Topics: Amino Acid Sequence; beta-Endorphin; Biological Assay; Endorphins; Humans; Pain; Receptors, Opioid; Structure-Activity Relationship

Topics: beta-Endorphin; Child; Endorphins; Female; Humans; Middle Aged; Pain; Pituitary Gland; Reflex

Topics: Adult; Aged; Analgesia; Animals; Anxiety; beta-Endorphin; Burns; Endorphins; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Narcotics; Neural Pathways; Neurotransmitter Agents; Pain; Receptors, Opioid; Receptors, Opioid, mu; Respiration, Artificial; Resuscitation; Sensory Thresholds; Stress, Physiological; Stress, Psychological; Time Factors

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Bombesin; Bradykinin; Cholecystokinin; Dynorphins; Endorphins; Enkephalins; Melanocyte-Stimulating Hormones; Mice; Nervous System; Neurotensin; Pain; Peptide Fragments; Peptides; Rats; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Vasopressins

Beta-endorphin-like immunoreactivity (i beta-EP) was measured in the CSF at myelography of 24 patients suspected of vertebral disk disease. Patients made several ratings of mood and pain for the 24 hours preceding myelography. Composite scores for pain, negative mood, and positive mood were derived by factor analysis. Pain Factor scores were negatively correlated with i beta-EP (r = -0.59, p less than 0.001), indicating a possible role for i beta-EP in the perception of the severity of pain. No significant correlation was shown between Positive or Negative Mood Factor scores and CSF i beta-EP. A physiologic indicator of pain severity is discussed.

Topics: beta-Endorphin; Emotions; Endorphins; Humans; Intervertebral Disc; Pain; Spinal Diseases

Topics: Adult; Aged; Analgesics; beta-Endorphin; Biological Availability; Chronic Disease; Endorphins; Female; Humans; Male; Middle Aged; Orosomucoid; Pain

Nine normally cycling women and seven other women employing oral contraception were tested during five phases (menstrual, follicular, ovulatory, luteal and premenstrual) of their menstrual cycle. The procedure consisted of administration of an anxiety inventory and determination of pain detection and pain thresholds in response to electric shock and the cold pressor task. Venipunctures were also performed and the plasma of normally menstruating women later assayed for beta-endorphin. Analyses revealed that the variance but not the mean levels in peripheral beta-endorphin levels significantly differed (p less than 0.01) across the menstrual cycle with the greatest amount of variance found during the ovulatory phase and the least during the luteal phase. The high variance during the period around ovulation was due to several subjects having extremely elevated beta-endorphin levels which possibly may have resulted from the occurrence of ovulation. Furthermore, a significant positive correlation between anxiety levels and beta-endorphin levels was found only during the menstrual phase. The absence of findings concerning cyclic variation in pain thresholds is contrary to earlier reports and indicates that such a phenomenon may be dependent upon the paradigm employed.. 9 mormally cycling women and 7 other women employing oral contraceptives (OCs) were tested during 5 phases (menstrual, follicular, ovulatory, luteal, and premenstrual) of their menstrual cycle. An anxiety inventory was administered and pain detection and pain thresholds in response to electric shock and the cold pressor task were determined. Venipunctures were also performed and the plasma of normally menstruating women later assayed for beta-endorphin. Analyses revealed that the variance but the not mean levels in peripheral beta-endorphin levels differed significantly (p0.01) across the menstrual cycle with the greatest amount of variance found during the ovulatory phase and the least during the luteal. The high variance during the period around ovulation was due to several subjects having extremely elevated beta-endorphin levels; this may have resulted from the occurrence of ovulation. Furthermore, a significant positive correlation between anxiety levels and beta-endorphin levels was found only during the menstrual phase. The absence of findings concerning cyclic variation in pain thresholds is contrary to earlier reports and indicates that such a phenomenon may be dependent on the paradigm employed.

Topics: Adult; Analysis of Variance; Anxiety; beta-Endorphin; Contraceptives, Oral; Differential Threshold; Endorphins; Female; Humans; Menstruation; Pain

Beta-Endorphin-like immunoreactivity in cerebrospinal fluid was assayed in 11 patients receiving electrical stimulation of the brain for chronic pain. Immunoreactivity increased dramatically after contrast ventriculography prior to stimulation. No further elevations were observed after stimulation. The magnitude and time course of elevations were identical after placement of electrodes either in the thalamus or in the periventricular gray matter. These results suggest that previous findings of stimulation-induced elevation of beta-endorphin-like immunoreactivity in cerebrospinal fluid are attributable to an artifact of contrast ventriculography.

Topics: Adult; Aged; beta-Endorphin; Cerebral Ventriculography; Contrast Media; Electronarcosis; Endorphins; Female; Humans; Male; Middle Aged; Pain; Pain Management; Radioimmunoassay

Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone.

Topics: Analgesia; Animals; beta-Endorphin; Biological Assay; Brain; Dose-Response Relationship, Drug; Endorphins; Kinetics; Mice; Naloxone; Pain; Receptors, Opioid; Structure-Activity Relationship

Long-term stimulation of deep brain structures for pain relief has been efficacious in a significant number of patients who have been total failures at every other means of pain control. Two primary sites are used at this time--the periventricular grey area, which is related to the endogenous opiate system, and the internal capsule system, which is related to the dorsal column projection system. Periventricular sites are more efficacious for externally generated pain, that is, pain with input through the dorsal horn. Internal capsule stimulation is more efficacious for central nervous system-generated pain. While the preoperative preparation and intraoperative testing as well as postoperative testing of these patients requires a great deal of time and tedious attention to detail, our long-term results have been excellent using a combined comprehensive pain unit approach to pain and stress management, plus the stimulation techniques in carefully selected patients. Our results would indicate that initially 80-85% of patients get good pain relief, and then that range decreases to between 50 and 60% over a long period of time. Deep brain stimulation for pain relief is not a technique that should be used on a large number of patients with simple pain problems, but is highly efficacious in a selected group of patients with very specific pain problems that do not respond to usual pain treatment techniques. In patients with pain generated by benign etiologies, it is far superior to destructive procedures and does not have the secondary side effects of sensory loss, postchordotomy dysesthesias, or secondary neurological deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: beta-Endorphin; Brain; Chronic Disease; Electronarcosis; Endorphins; Ganglia, Spinal; Humans; Pain; Pain Management; Prognosis; Serotonin; Spinal Cord; Stereotaxic Techniques

Bilateral, radio-frequency destruction of the ventro-medial posterior hypothalamus (VMPH) resulted, as compared to sham-operated and control rats and evaluated in the tail-flick and vocalization tests, in a significant decrease in basal nociceptive threshold on day 4 post-surgery. By day 12, however, no significant difference between sham and lesioned rats was seen. At this time the antinociception elicited by either acute foot-shock or cold-water-immersion stress was profoundly attenuated. The antinociceptive response to various doses of morphine was not, in contrast, diminished. As established by use of radioimmunoassay, these lesions did not significantly alter hypothalamic levels of beta-endorphin, met-enkephalin, dynorphin or alpha-neo-endorphin. They did, however, produce a pronounced and significant fall in the hypothalamic content of substance P. These data are indicative that the VMPH may, via a mechanism not involving endorphins, be of importance in the determination of basal nociceptive threshold and in the generation of stress-, but not morphine-, evoked antinociception. The relationship of these findings to the interconnections of the VMPH, and to the possible significance of substance P and the pituitary in nociceptive processes, is discussed.

Topics: Animals; beta-Endorphin; Dynorphins; Electroshock; Endorphins; Enkephalin, Methionine; Hypothalamus; Hypothalamus, Posterior; Male; Morphine; Naltrexone; Nociceptors; Pain; Protein Precursors; Rats; Rats, Inbred Strains; Stereotaxic Techniques

In twenty patients with chronic pain syndrome, acupuncture treatment resulted in significant improvement of both pain and psychiatric symptoms and higher plasma concentrations of metenkephalin. Plasma beta-endorphin concentrations were unchanged. The degree of symptom relief was correlated with the increase in plasma met-enkephalin.

Topics: Acupuncture Therapy; beta-Endorphin; Chronic Disease; Endorphins; Enkephalin, Methionine; Female; Humans; Male; Mental Disorders; Pain; Pain Management; Syndrome

Beta-endorphin and related opioid peptides are neuropeptides which appear to play a role in cardiovascular regulation which is supported by altered nociceptive responsiveness in hypertensive animals. In spontaneously hypertensive rats the pain threshold for electric stimulation is elevated; these rats show increased response latency time in a hot plate test. The opiate antagonist naloxone reverses these values to that of the normotensive controls. In other forms of experimental hypertension, eg, renal hypertension (one-clip, two-kidney model), no change in pain sensitivity is apparent. Sinoaortic baroreceptor denervation causes a labile hypertension without changes in hot plate response. Administration of beta-endorphin into the nucleus of the solitary tract (NTS) gradually decreases blood pressure and heart rate without affecting respiratory frequency. These cardiovascular effects are blocked by naloxone as well as by an antibody to beta-endorphin. In contrast to the effects of beta-endorphin, microinjection of enkephalins into the NTS increases blood pressure and heart rate. The data suggest the existence of two separate endorphin systems at the level of the NTS, one a depressor and another a pressor system. The depressor influence of beta-endorphin may play a role in the mechanism of action of antihypertensive agents such as methyldopa and clonidine. Our data support a role of endorphins as neuropeptides involved in cardiovascular regulation, exerting a dual influence at the level of the NTS.

Topics: Animals; beta-Endorphin; Blood Pressure; Brain; Endorphins; Enkephalins; Heart Rate; Hypertension; Male; Medulla Oblongata; Naloxone; Nociceptors; Pain; Rats; Sensory Thresholds

The objectives of this study were threefold. First, we investigated the effects of acute stressful stimuli on gastroduodenal feeding activity after a physiologic meal. Second, we explored the possible role of humoral mediators of these effects by measuring concurrently plasma levels of beta-endorphin, catecholamines, and several gut peptides. Third, we wished to determine whether or not the gut responded selectively to different types of central stimuli. Thus, in 12 healthy volunteers we studied the effects of vertigo and cold pain on the gastrointestinal motor response to a solid meal. Pressure activity was recorded by a low-compliance perfusion system. Plasma concentrations of beta-endorphin and gut peptides were measured by radioimmunoassay, whereas catecholamine levels were measured by high-pressure liquid chromatography. Blood pressure, pulse rate, and skin conductance were also monitored. Labyrinthine vertigo (by otic stimulation with 10 degrees C water; control, 37 degrees C water) and cold pain (immersing hand in 4 degrees C water; control, 37 degrees C water) were simultaneously induced after the meal in each subject according to a 2 X 2 factorial experimental design. Cold pain and labyrinthine stimulation alone or in combination significantly reduced the antral phasic pressure response to solids while elevating plasma levels of beta-endorphin and norepinephrine. These effects occurred within the first 20 min poststimulus and were associated with changes in blood pressure, pulse rate, and skin conductance. Further, in 2 of 6 individuals in whom vertigo was induced by labyrinthine stimulation, a phase 3-like burst of motor activity appeared in the duodenum and migrated aborally. We conclude that centrally acting external stimuli may severely disrupt antral feeding activity. Furthermore, concurrent elevations in plasma levels of beta-endorphin and norepinephrine raise the possibility that these substances may be involved as mediators of the central effects on the gut.

Topics: Adult; beta-Endorphin; Chromatography, High Pressure Liquid; Cold Temperature; Digestion; Eating; Endorphins; Female; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Male; Manometry; Middle Aged; Motor Activity; Norepinephrine; Pain; Pressure; Radioimmunoassay; Stress, Physiological; Vertigo

Chronic dorsal periaqueductal grey matter electrodes were implanted into adult rats under pentobarbitone anaesthesia. Stimulating these electrodes (25-300 microA) produced behavioural analgesia in 23 of 44 rats tested. In rats given the opiate antagonist naloxone attenuation of this analgesia was seen. In 14 rats displaying behavioural analgesia to periaqueductal grey matter stimulation acute electrophysiological experiments were performed under urethane anaesthesia. Microelectrode recordings were made from neurones, excited by noxious heat or pinch applied to the limbs and tail, and located in the reticular formation of the caudal medulla. Stimulation of the periaqueductal grey matter at an intensity sufficient to produce analgesia in the conscious animal produced direct inhibition of the firing of 62% of neurones tested, excited 23%, had no effect on 14% and attenuated the nociceptive responses of 66%. The inhibitions were characteristically long. Local application of naloxone by microiontophoresis attenuated these long inhibitions in 11 out of 16 neurons tested. Immunohistochemical localization of beta-endorphin containing structures in the vicinity of stimulating and recording sites suggested that the naloxone sensitive inhibition of nociceptive neuronal responses in caudal medulla reticular formation may be due to activation of beta-endorphin fibres descending through the periaqueductal area to the caudal medulla.

Topics: Action Potentials; Analgesia; Animals; beta-Endorphin; Cerebral Aqueduct; Electric Stimulation; Endorphins; Hindlimb; Male; Medulla Oblongata; Naloxone; Pain; Physical Stimulation; Rats; Reticular Formation; Tail

Decapeptide ceruletide (CRL), chemically related to cholecystokinin and gastrin, proved to have remarkable analgesic properties when administered to a group of 22 burned patients, 15 patients with acute myocardial infarction, and 8 patients suffering from pain caused by malignant tumours with metastases. Its effect was such, that many of the patients required no other analgesics (opiates) even after a prolonged administration (up to 10 days) of CRL. In some of the patients a marked euphoria developed. There were no substantial changes in EEG records during CRL administration in 15 controls, among them 4 epileptics. It is probable that CRL helps to activate the internal analgesic system. In the burned patients cortisol, testosterone, renin, prolactin and tri-iodothyronine (T3) levels in serum (plasma) were measured (radio-immunoassays). CRL did not block the stress response (no drop of increased cortisol levels, no increase in low T3 levels), but it modified (influenced) it (drop of the high renin levels, and a tendency to increase the very low testosterone levels). CRL appears to act as an endorphin releaser, as evidenced by the plasma levels of beta-endorphins (quotations). CRL and similar drugs may represent a new, more physiological and probably safer approach to the management of pain.

Topics: beta-Endorphin; Burns; Ceruletide; Endorphins; Humans; Male; Myocardial Infarction; Neoplasm Metastasis; Neoplasms; Pain

This study compared basal concentrations of plasma beta-endorphin/beta-lipotropin-like immunoreactivity and dexamethasone suppression of cortisol in seven chronic pain patients, seven psychiatric disorder patients, and seven normal volunteers. Pain patients and psychiatric patients showed significantly higher basal concentrations of beta-endorphin/beta-lipotropin-like immunoreactivity compared to normal volunteers. Pain patients also had significantly higher beta-endorphin/beta-lipotropin-like immunoreactivity than psychiatric patients, even though there was no significant difference in severity of depressive symptomatology as assessed by Beck and Hamilton scores. Resistance to dexamethasone occurred in 57% of pain patients. These results may indicate that biological markers for depression occur in populations of chronic pain patients, or may reflect levels of central nervous system arousal in response to stress, pain, or nonaffective phenomena.

Topics: Adult; Alcoholism; beta-Endorphin; beta-Lipotropin; Chronic Disease; Depression; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Male; Mental Disorders; Middle Aged; Mood Disorders; Pain; Radioimmunoassay; Syndrome

The role of opioid peptides during pregnancy and parturition has not been defined. They may function as natural analgesics during parturition. Pain thresholds were tested during pregnancy but, in contrast with a previous study, were found not to change. Plasma Beta-endorphin-like-immunoreactivity (B-ELI) was measured and towards the end of pregnancy a significant increase was recorded. Peptide levels returned to the pre-gestational concentration just prior to parturition. Pituitary B-ELI was also measured and was only significantly raised on the day before expected parturition. These changes add to the evidence that opioid peptides have a physiological function during pregnancy and parturition.

Topics: Animals; beta-Endorphin; Endorphins; Female; Pain; Pituitary Gland; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains; Sensory Thresholds; Time Factors

Epidural administration of 3 mg of synthetic beta-endorphin produced analgesia in 10 patients with intractable pain due to disseminated cancer. Mean onset of relief of pain was 24 +/- 3 minutes and the mean duration of analgesia was 19 +/- 3 hours. The onset of analgesia produced by the epidural injection of beta-endorphin was slower and the duration less than those observed after intrathecal injection.

Topics: Adult; Aged; beta-Endorphin; Endorphins; Epidural Space; Female; Humans; Injections; Male; Middle Aged; Neoplasms; Pain

Endogenous opiates have been implicated in pain and stress experiences. In order to directly assess the relationship between endorphin activity and acute behavioral distress, beta-endorphin immunoreactivity (beta-EPI) was measured by radioimmunoassay in cerebrospinal fluid of 75 children with acute leukemia undergoing routine lumbar puncture. These data were related to four measures of behavioral distress collected during the procedure. For children 4 years of age and above, beta-EPI correlated inversely with age (r = -.31,p less than or equal to .05). All behavioral measures also inversely correlated with age (r = -.26 to -.67,p less than or equal to .05 to .001). Females had a significantly lower mean beta-EPI than males (p less than or equal to .01), and exhibited greater behavioral distress. beta-EPI and behavioral measures interacted with the use of specific antileukemia agents. L-Asparaginase was associated with lower beta-EPI (p less than or equal to .05), while prednisone was associated with lower behavioral distress on three of the four measures (p less than or equal to .05 to .01). After controlling for age, sex, and chemotherapy, beta-EPI and nurse ratings of anxiety were positively correlated (partial correlation coefficient = .31, p less than or equal to .05). Correlations between beta-EPI and other behavioral measures demonstrated positive trends. Results of this study are interpreted as support for the reactive nature of beta-EPI in cerebrospinal fluid to acute distress, and may help explain documented sex differences in distress behavior. Potential clinical implications and directions for further research are discussed.

Topics: Adolescent; Age Factors; beta-Endorphin; Child; Child, Preschool; Endorphins; Female; Humans; Infant; Leukemia, Lymphoid; Male; Pain; Radioimmunoassay; Sex Factors; Spinal Puncture; Stress, Psychological

Plasma beta-endorphin-like immunoreactivity (beta-ELI) was measured at intervals during labour in 42 patients. An increase in beta-ELI occurred during labour and increased to a maximum during the second stage. The increase in beta-ELI paralleled dilatation of the cervix. A correlation existed between the duration of labour and second stage beta-ELI in patients with labours of more than 4 h duration. Analgesic drugs were associated with changes in beta-ELI. The patients who received Entonox had greater plasma beta-ELI concentrations than those who received pethidine. A significant difference in the second stage beta-ELI existed between those who received only Entonox and those who received only pethidine. Induction and augmentation of labour were also associated with differences in beta-ELI. Patients in spontaneous labour had significantly lower beta-ELI than patients who had either artificial rupture of membranes or Syntocinon augmentation of labour.

Topics: Adolescent; Adult; Anesthesia, Inhalation; Anesthesia, Obstetrical; beta-Endorphin; Endorphins; Female; Humans; Labor, Induced; Labor, Obstetric; Meperidine; Pain; Pregnancy; Time Factors

1. We examined the effect of ischaemic pain and sustained isometric muscle contraction on plasma immunoreactive gamma-lipotropin (gamma LPH), beta-endorphin/beta-lipotropin (beta END/beta LPH) and corticotropin (ACTH), which are all synthesized from a common precursor (pro-opiocortin), and plasma cortisol in 10 normal subjects. 2. Experimental pain was produced by inflation to 250 mmHg of a sphygmomanometer cuff, placed above the elbow of the 'dominant' arm, after which the subject squeezed a hand dynamometer, loaded to 12 kg, 20 times at 2 s intervals. Blood was drawn before, after 5 and 10 min of pain, and 30 min after release of the cuff. In a control session, the subjects were asked to squeeze the handgrip alone for 5 min at 30% of their maximum strength, a procedure which elevates the blood pressure without causing pain. 3. One subject had unexplained high (30--71 pmol/l) baseline peptide concentrations. Baseline values for the nine other subjects were: ACTH, 7.3 +/- 1.9 pmol/l (mean +/- SEM); gamma LPH, 18.6 +/- 1.0 pmol/l; beta END/beta LPH, 10.0 +/- 1.1 pmol/l; cortisol, 599 +/- 55 nmol/l. Neither procedure significantly increased the plasma concentration of ACTH or any other peptide, whereas plasma cortisol was significantly increased at both 5 min and 10 min. Plasma ACTH was positively correlated with plasma gamma LPH (r = 0.701; P less than 0.001), beta END/beta LPH (r = 0.970; P less than 0.001) and plasma cortisol (r = 0.758; P less than 0.05). 4. The present study demonstrates that, in normal man, plasma endorphins do not change with experimental ischaemic pain. The rise in plasma cortisol without concomitant rise in ACTH is not explained, but suggests the action of some other agent at the level of the adrenal cortex.

Topics: Adrenocorticotropic Hormone; Adult; Arm; beta-Endorphin; beta-Lipotropin; Endorphins; Female; Humans; Hydrocortisone; Ischemia; Male; Middle Aged; Pain; Radioimmunoassay; Time Factors

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Endorphins; Injections, Spinal; Male; Morphine; Pain; Rats; Rats, Inbred Strains; Spinal Cord

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Pressure; Brain; Digestive System; Endorphins; Humans; Hypertension; Morphine; Pain; Pituitary Gland; Receptors, Opioid; Shock

Topics: Arthritis; beta-Endorphin; Endorphins; Female; Humans; Male; Pain

The thiolcarboxyl peptide [17-thiolglycine]-beta-endorphin-(1-17) (I) was synthesized by the solid-phase method. Reaction of peptide I with citraconic anhydride gave citraconyl-[Lys(Cit9,GlyS17]-beta-endorphin-(1-17) (Ia). Peptide Ia was coupled to another synthetic peptide, [Lys(Cit)19,24,28,29]-beta-endorphin-(18-31), by reaction with silver nitrate--N-hydroxysuccinimide in water. All citraconyl groups were removed in aqueous acetic acid, and [Gly17]-beta-endorphin was isolated in 30-40% yield. The synthetic analog had 10% analgesic potency and 59% opiate--receptor binding activity when compared with human beta-endorphin.

Topics: Amino Acid Sequence; Animals; beta-Endorphin; Biological Assay; Endorphins; Humans; Methods; Mice; Oligopeptides; Pain; Structure-Activity Relationship

Topics: Analgesia; Angiotensin II; beta-Endorphin; Cholecystokinin; Endorphins; Enkephalins; Humans; Neurotensin; Neurotransmitter Agents; Pain; Peptides; Somatostatin; Substance P

Topics: Animals; beta-Endorphin; Brain; Endorphins; Enkephalins; Humans; Pain; Pituitary Gland; Rats; Receptors, Opioid