pituitrin and Pain

Oxytocin and vasopressin are neurohypophyseal hormones with sequence similarity and play a central role in bodily homeostatic regulation. Pain is currently understood to be an important phenotype that those two neurohormones strongly downregulate. Nociceptors, the first component of the ascending neural circuit for pain signals, have constantly been shown to be modulated by those peptides. The nociceptor modulation appears to be critical in pain attenuation, which has led to a gradual increase in scientific interest about their physiological processes and also drawn attention to their translational potentials. This review focused on what are recently understood and stay under investigation in the functional modulation of nociceptors by oxytocin and vasopressin. Effort to produce a nociceptor-specific view could help to construct a more systematic picture of the peripheral pain modulation by oxytocin and vasopressin.

Topics: Humans; Nociceptors; Oxytocin; Pain; Receptors, Oxytocin; Receptors, Vasopressin; Vasopressins

Autosomal dominant polycystic kidney disease (ADPKD), which frequently leads to end-stage renal disease, currently has no specific drug therapies. Better understanding of its pathogenesis and recent clinical trials have led to more accurate diagnosis of the disease and its manifestations, as well as to promising new approaches to treatment.

Topics: Drug Discovery; Humans; Hypertension; Intracranial Aneurysm; Pain; Polycystic Kidney, Autosomal Dominant; Signal Transduction; TOR Serine-Threonine Kinases; Urinary Tract Infections; Vasopressins

Vasovagal syncope is defined as a reflex loss of consciousness related to reaction to various stimuli as orthostatic stress, pain or emotions connected with loss of muscle postural tone. The aetiology of this disorder is still unknown. The imbalance between the parts of autonomic nervous system and other homeostasis-related systems as renin-angiotensin-aldosterone system, peptides as endothelin, neuropeptide Y, vasopressin, adrenomedullin and cAMP, adenosine and AMP can play an important role in the development of vasovagal syncope. In the first part of the paper the authors describe the mechanisms involved in the development of vasovagal reaction, pathophysiology of the head-up tilt test and the role of autonomic nervous system.

Topics: Adrenomedullin; Cyclic AMP; Endothelins; Humans; Muscle Hypotonia; Neuropeptide Y; Pain; Peptides; Posture; Receptors, Neurotransmitter; Renin-Angiotensin System; Syncope, Vasovagal; Vasopressins

The authors highlight the potential importance of neuropeptides as clinical tools in the study and treatment of pain. Although many questions remain unanswered, it is encouraging that several clinical and experimental advances have shed new light on the neuropharmacology of nociception and have prompted new hope for more effective treatments of such diverse problems as chronic intractable pain, migraine, and drug dependency. Within the next few years, it is anticipated that further work in this area will lead to better basic and clinical understanding of these important clinical problems.

Topics: Animals; Bombesin; Bradykinin; Calcitonin; Central Nervous System; Cholecystokinin; Endorphins; Neurons, Afferent; Neuropeptides; Neurotensin; Pain; Somatostatin; Substance P; Vasopressins

Topics: Animals; Appetite; APUD Cells; Biological Evolution; Blood Pressure; Body Temperature Regulation; Cell Differentiation; Central Nervous System; Chemical Phenomena; Chemistry; Cricetinae; Endorphins; Humans; Immunity; Memory; Mental Disorders; Mice; Nerve Tissue Proteins; Neurotransmitter Agents; Pain; Rats; Synaptic Transmission; Vasopressins

Topics: Analgesia; Animals; Cold Temperature; Deoxyglucose; Endorphins; Hyperphagia; Hypophysectomy; Hypothalamus; Morphine; Naloxone; Pain; Physical Exertion; Rats; Rats, Brattleboro; Sensory Thresholds; Stress, Physiological; Vasopressins

Topics: Adaptation, Psychological; Appetite; Biological Evolution; Blood Pressure; Body Temperature Regulation; Brain; Carboxypeptidases; Cell Count; Central Nervous System Diseases; Chemical Phenomena; Chemistry, Physical; Chromaffin Granules; Dissection; Electrophysiology; Histocytochemistry; Humans; Immunochemistry; Learning; Memory; Nerve Tissue Proteins; Neural Pathways; Neuroanatomy; Pain; Peptides; Psychotic Disorders; Radioimmunoassay; Receptors, Cell Surface; Stereotaxic Techniques; Tissue Distribution; Vasopressins

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Topics: Alzheimer Disease; Animals; Brain; Cholecystokinin; Choline O-Acetyltransferase; Endorphins; Epilepsy; Forecasting; Histocytochemistry; Humans; Huntington Disease; Migraine Disorders; Nerve Tissue Proteins; Nervous System Diseases; Pain; Parkinson Disease; Radioimmunoassay; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Tissue Distribution; Vasopressins

Anatomical studies have suggested that the posterior pituitary peptide, vasopressin (VP, antidiuretic hormone) may be released at central neural sites other than the neurohypophysis. Immunohistochemical techniques allow VP to be visualized at numerous sites in the central nervous system (CNS). VP can also be measured in cerebrospinal fluid (CSF). Some of the stimuli which evoke VP release from the posterior pituitary may also elevate CSF VP levels. VP may play an important part in a variety of CNS functions. Substantial evidence exists implicating VP in learning and memory processes. VP may have a role in cardiovascular regulation through central pathways. Further, VP appears to act on the regulation of body temperature during fever. Other areas of central regulation where VP may be important include circadian rhythmicity, control of water intake, control of permeability of brain capillaries to water, central regulation of ACTH release and nociception. It appears that at least some of these central effects of VP involve an interaction with catecholaminergic neurotransmission.

Topics: Animals; Blood-Brain Barrier; Body Temperature Regulation; Cardiovascular System; Catecholamines; Central Nervous System; Circadian Rhythm; Dogs; Hypertension; Learning; Memory; Pain; Paraventricular Hypothalamic Nucleus; Rabbits; Rats; Rats, Brattleboro; Supraoptic Nucleus; Synaptic Transmission; Vasopressins; Water-Electrolyte Balance

Topics: Analgesia; Angiotensin II; Bombesin; Bradykinin; Cholecystokinin; Endorphins; Humans; Nerve Tissue Proteins; Neurotensin; Oligopeptides; Pain; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide; Vasopressins

To date about thirty peptides--low-molecular-weight, single-chain amino acid compounds--are known to be distributed widely in the central nervous system within selective neuron pathways. These findings, combined with a large body of neuropharmacological, behavioral, and electrophysiological data, open new horizons in neurobiology, force a reexamination of old and accepted hypotheses, and hold important implications for the clinician. There is evidence that substance P and the opioid peptides play a major role in the pain pathway, particularly at the level of the spinal cord. Available evidence also implicates vasoactive intestinal polypeptide in the control of cerebral circulation, cholecystokinin in the regulation of appetite, and vasopressin and adrenocorticotropic hormone in memory. Many questions, however, remain. For most peptides there is little information on mechanisms of biosynthesis, release, interaction with receptors, and termination of biological effect. Another important question is the interaction of peptides with other neurotransmitters. The evidence that both "classic" neurotransmitters and peptides can be found in the same neuronal necessitates reformulation of Dale's "one neuron, one neurotransmitter" hypothesis. It may be that a single cell, while containing different classes of neurotransmitter, will contain only one member of any particular class. It is not too early to speculate on the role of the numerous and diverse peptides in neuronal tissue and on the implications of peptide abnormalities in a variety of neurological diseases. The answers to these and other questions pose a fascinating challenge to neurobiologist and clinician alike.

Topics: Adrenocorticotropic Hormone; Animals; Appetite; Brain; Brain Chemistry; Brain Mapping; Cerebrovascular Circulation; Cholecystokinin; Enkephalins; Humans; Memory; Mesencephalon; Mice; Neural Pathways; Pain; Peptides; Rats; Spinal Cord; Substance P; Vasoactive Intestinal Peptide; Vasopressins

Several lines of evidence suggest that the endogenous opioid peptides endorphins may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as evidence linking endorphins to the anterior pituitary polypeptide hormone adrenocorticotropin (ACTH). Evidence is presented that endorphins may function as trophic hormones in peripheral target organs such as the adrenal medulla and the pancreas. As such they may be part of the physiological mechanisms that mediate adrenaline and glucagon release in response to stress. Endorphins (enkephalins) are also suggested to play a role in the control of the pituitary gland during stress. In such capacity they may act as hormone-releasing or inhibiting factors. Finally, endorphins appear to play a role in the behavioral concomitants of stress. In such capacity endorphins are suggested to function as modulators of neural systems that mediate the elaboration and expression of the reactive/affective components of stress. Speculations on the mode of interaction between endorphins and ACTH in the global response to stress are discussed.

Topics: Adaptation, Physiological; Adrenal Medulla; Adrenocorticotropic Hormone; Animals; Chemical Phenomena; Chemistry; Emotions; Endorphins; Epinephrine; Glucagon; Humans; Hypothalamo-Hypophyseal System; Insulin; Islets of Langerhans; Naloxone; Pain; Pituitary Gland; Pituitary-Adrenal System; Rats; Receptors, Opioid; Stress, Physiological; Stress, Psychological; Vasopressins

Topics: Abdomen; Autonomic Nervous System; Axons; Constipation; Cranial Nerves; Depression; Diabetic Neuropathies; Drug Interactions; Hallucinations; Humans; Hyponatremia; Hypotension, Orthostatic; Intestinal Obstruction; Muscular Atrophy; Nervous System Diseases; Neural Conduction; Norepinephrine; Pain; Paresthesia; Parkinson Disease; Peripheral Nervous System Diseases; Seizures; Vasopressins; Vincristine

The local analgesic efficacy of a cream formulation of lidocaine and prilocaine (EMLA) in reducing pain at venous cannulation was investigated in children scheduled for elective surgery. Forty children participated in a double-blind, randomized comparison between EMLA and inactive placebo cream. Another group of 18 children without any local treatment was studied as an additional control material. Subjective pain scores, expressed with a visual analogue scale, were significantly lower in the EMLA group compared with both the group treated with placebo cream (P less than 0.001) and the open control group (no cream; P less than 0.01). Local pallor and slight oedema were the only side-effects, registered in both cream-treated groups. A preliminary study was also carried out with 10 children (five with EMLA and five without) in order to determine whether catecholamine and vasopressin levels in venous blood are affected by the stress and anxiety associated with venepuncture in children premedicated with oral flunitrazepam. No significant hormone responses were, however, detected. The lidocaine concentrations measured in venous blood taken from the application site of EMLA cream were low, and there were no measurable levels of lidocaine in simultaneous blood samples from the opposite extremity. In our opinion EMLA cream is safe and alleviates effectively the pain associated with venepuncture, and thus deserves a place in the routine premedication of children.

Topics: Administration, Cutaneous; Anesthetics, Local; Anxiety; Catecholamines; Catheterization, Peripheral; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Ointments; Pain; Pain Measurement; Preanesthetic Medication; Prilocaine; Random Allocation; Vasopressins

Thirty two male patients undergoing coronary bypass surgery were given low (group A, 0.01 mg/kg bw) and high dose (group B, 0.035 mg/kg bw) fentanyl anaesthesia. Haemodynamic and hormone responses were investigated from the beginning of anaesthesia until extracorporeal circulation (ECC) (group A: n = 16; group B: n = 16). Significant changes in haemodynamics occurred only in group A including an increase in heart rate (36%) and systolic arterial pressure (21%). Plasma vasopressin (ADH) levels rose significantly in both groups after the beginning or surgical procedure which was markedly less pronounced in patients with high fentanyl (group B). In group A (low dose) a second dose of fentanyl was given after sternotomy, which was followed by a significant decrease in ADH (80% from previous value). No significant variations could be demonstrated in plasma levels of cortisol, ACTH, and human growth hormone (HGH). The data stress the importance of plasma-vasopressin-levels in determining the endocrine stress response following trauma and operation. On the other hand there was a lack of correlation between trauma and pain and frequently reported patterns of the endocrine-metabolic stress response.

Topics: Adrenocorticotropic Hormone; Adult; Anesthesia, General; Clinical Trials as Topic; Coronary Artery Bypass; Fentanyl; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Pain; Prospective Studies; Random Allocation; Stress, Physiological; Vasopressins

Topics: Adult; Anesthesia, Dental; Clinical Trials as Topic; Epinephrine; Female; Humans; Ischemia; Male; Mepivacaine; Microcirculation; Middle Aged; Ornithine; Pain; Regional Blood Flow; Time Factors; Vasopressins

Topics: Herpes Zoster; Humans; Pain; Syndrome; Trigeminal Nerve; Vasopressins

To report on an unusual case of ketamine-precipitated syndrome of inappropriate antidiuretic hormone secretion (SIADH) in an individual managed by an outpatient pain specialty team.. A 78-yr-old male presented to the emergency department with lethargy, malaise, nausea, and abdominal bloating three days following intravenous ketamine infusion for intractable postsurgical lumbar radicular pain with neuropathic features. The patient had a history of resected prostate cancer, hyperlipidemia, chronic kidney disease, and spinal stenosis and the cause of his symptoms was investigated. He was found to be hyponatremic and the treating team excluded reversible surgical and medical causes. A Naranjo score of 7 was calculated, suggesting that the correlation between ketamine and hyponatremia was "likely." Hence, a diagnosis of ketamine-precipitated SIADH was made. The patient was treated with fluid restriction and symptoms were controlled with antiemetics. He returned to baseline function with resolution of the hyponatremia within three days of discharge.. This case is of clinical importance for providers using ketamine in the field of pain management as the effect of this medication reaction can be profound. Clinicians should develop an awareness that ketamine can potentiate adverse effects such as SIADH and they should monitor, detect, and manage as appropriate.. RéSUMé: OBJECTIF: Nous signalons un cas inhabituel de syndrome de sécrétion inappropriée d’hormones antidiurétiques (SIADH - syndrome of inappropriate antidiuretic hormone secretion) précipité par la kétamine chez une personne prise en charge par une équipe spécialisée en douleur en soins ambulatoires. CARACTéRISTIQUES CLINIQUES: Un homme de 78 ans s’est présenté à l’urgence souffrant de léthargie, de malaise, de nausées et de ballonnements abdominaux trois jours après avoir reçu une perfusion intraveineuse de kétamine pour le traitement d’une douleur radiculaire lombaire postopératoire rebelle avec des caractéristiques neuropathiques. Le patient avait des antécédents de résection de cancer de la prostate, d’hyperlipidémie, d’insuffisance rénale chronique et de sténose du canal rachidien, et la cause de ses symptômes a été évaluée. Il s’est avéré hyponatrémique et l’équipe soignante a exclu les causes chirurgicales et médicales réversibles. Un score Naranjo de 7 a été calculé, suggérant que la corrélation entre la kétamine et l’hyponatrémie était « probable ». Par conséquent, un diagnostic de SIADH précipité par la kétamine a été posé. Le patient a été traité par restriction hydrique et les symptômes ont été contrôlés par des antiémétiques. Il est revenu à son fonctionnement de référence avec la résolution de l’hyponatrémie dans les trois jours suivant son congé. CONCLUSION: Ce cas est important d’un point de vue clinique pour les praticiens qui utilisent la kétamine pour la prise en charge de la douleur, car l’effet de cette réaction médicamenteuse peut être profond. Les cliniciens devraient prendre conscience que la kétamine peut augmenter des effets indésirables tels que le SIADH et ils devraient monitorer, dépister et prendre en charge le patient, le cas échéant.

Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Hyponatremia; Inappropriate ADH Syndrome; Ketamine; Male; Pain; Vasopressins

Recent research has revealed that the community of microorganisms inhabiting the gut affects brain development, function and behaviour. In particular, disruption of the gut microbiome during critical developmental windows can have lasting effects on host physiology. Both antibiotic exposure and germ-free conditions impact the central nervous system and can alter multiple aspects of behaviour. Social impairments are typically displayed by antibiotic-treated and germ-free animals, yet there is a lack of understanding of the underlying neurobiological changes. Since the μ-opioid, oxytocin and vasopressin systems are key modulators of mammalian social behaviour, here we investigate the effect of experimentally manipulating the gut microbiome on the expression of these pathways.. We show that social neuropeptide signalling is disrupted in germ-free and antibiotic-treated mice, which may contribute to the behavioural deficits observed in these animal models. The most notable finding is the reduction in neuroreceptor gene expression in the frontal cortex of mice administered an antibiotic cocktail post-weaning. Additionally, the changes observed in germ-free mice were generally in the opposite direction to the antibiotic-treated mice.. Antibiotic treatment when young can impact brain signalling pathways underpinning social behaviour and pain regulation. Since antibiotic administration is common in childhood and adolescence, our findings highlight the potential adverse effects that antibiotic exposure during these key neurodevelopmental periods may have on the human brain, including the possible increased risk of neuropsychiatric conditions later in life. In addition, since antibiotics are often considered a more amenable alternative to germ-free conditions, our contrasting results for these two treatments suggest that they should be viewed as distinct models.

Topics: Animals; Anti-Bacterial Agents; Brain; Gastrointestinal Microbiome; Mice; Neuropeptides; Pain; Social Behavior; Vasopressins

Frequencies of single nucleotide polymorphisms (SNPs) from pain related candidate genes are available for individuals with sickle cell disease (SCD). One of those genes, the arginine vasopressin receptor 1A gene (AVPR1A) and one of its SNPs, rs10877969, has been associated with pain and disability in other pain populations. In patients with SCD, clinical factors such as pain and stress have been associated with increased health care utilization, but it is not known if the presence of the AVPR1A SNP plays a role in this observation. The study purpose was to explore the relationships between rs10877969 and self-reported pain, stress, and acute care utilization events among individuals with SCD.. In a cross-sectional investigation of outpatients with SCD, participants completed PAINReportIt®, a computerized pain measure, to describe their pain experience and contributed blood or saliva samples for genetic analysis. We extracted emergency department and acute care utilization from medical records.. The SNP genotype frequencies (%) for this sample were CC 30 (28%), CT 44 (41%), TT 33 (31%). Acute care utilization and stress as an aggravator of pain were significantly associated with the rs10877969 genotype (p = .02 and p = .002, respectively). The CT genotype had the highest mean utilization and CC genotype was associated with not citing stress as a pain aggravator. Chronic pain was not associated with rs10877969 (p = .41).. This study shows that rs10877969 is related to indicators of stress and acute pain. Further research is recommended with other measures of stress and acute pain.

Topics: Adult; Aged; Anemia, Sickle Cell; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Pain; Polymorphism, Single Nucleotide; Stress, Psychological; Vasopressins; Young Adult

Oxytocin (OT) continues to inspire much research due to its diverse physiological effects. While the best-understood actions of OT are uterine contraction and milk ejection, OT is also implicated in maternal and bonding behaviors, and potentially in CNS disorders such as autism, schizophrenia, and pain. The dissection of the mechanism of action of OT is complicated by the fact that this peptide activates not only its cognate receptor but also vasopressin type 1a (V1a) receptors. In this study, we evaluated OT and a selective OT receptor (OTR) agonist, FE 204409, in an automated assay that measures rat locomotor activity. The results showed: 1) Subcutaneous (sc) administration of OT decreased locomotor behavior (distance traveled, stereotypy, and rearing). This effect was reversed by a V1a receptor (V1aR) antagonist ([Pmp1,Tyr(ME)2]AVP, sc), suggesting that OT acts through peripheral V1aR to inhibit locomotor activity. 2) A selective OTR agonist (FE 204409, sc) increased stereotypy. This effect was reversed by an OTR antagonist dosed icv, suggesting a central OTR site of action. Our findings identify distinct behavioral effects for OT and the selective agonist FE 204409, adding to the growing body of evidence that the V1aR mediates many effects attributed to OT and that peptides administered systemically at supra-physiological doses may activate receptors in the brain. Our studies further emphasize the importance of utilizing selective agonists and antagonists to assess therapeutic indications.

Topics: Animals; Behavior, Animal; Locomotion; Male; Oxytocin; Pain; Rats, Sprague-Dawley; Receptors, Oxytocin; Receptors, Vasopressin; Social Behavior; Vasopressins

Topics: Adrenal Insufficiency; Adult; Amputation, Surgical; Anti-Bacterial Agents; Disseminated Intravascular Coagulation; Epoprostenol; Escherichia coli; Escherichia coli Infections; Female; Gangrene; Humans; Hydrocortisone; Hypotension; Kidney Calculi; Leg; Metatarsus; Pain; Platelet Aggregation Inhibitors; Purpura Fulminans; Shock, Septic; Vasopressins

Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog desmopressin revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was only observed in nonstressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent, to the best of our knowledge, the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.

Topics: Analgesics; Animals; Animals, Newborn; Capsaicin; Deamino Arginine Vasopressin; Disease Models, Animal; Female; Genetic Association Studies; Habituation, Psychophysiologic; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Weight; Pain; Pain Measurement; Pain Threshold; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Receptors, Vasopressin; Sex Factors; Stress, Psychological; Vasopressins

Topics: Analgesics; Animals; Female; Humans; Male; Pain; Pain Threshold; Vasopressins

Little is known about the chemical coding of the brain neuronal circuitry activated by nociceptive signals of visceral origin. We characterized brain nuclei activated during isovolumetric phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) in conscious male rats, using Fos as a marker of neuronal activation and dual immunohistochemistry to visualize co-localization of Fos expression and oxytocin (OT), arginine-vasopressin (AVP), corticotrophin-releasing factor (CRF) or tyrosine hydroxylase (TH). Proximal colon distension, compared with sham distension, induced a robust increase in Fos-like immunoreactive (IR) neurons in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and accessory neurosecretory nuclei of the hypothalamus, nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), and to a lower extent, in the locus coeruleus (LC) and Barrington nucleus. Fos-IR neurons in the PVN after colon distension were identified in 81% of OT-IR, 18% AVP-IR and 16% CRF-IR neurons, while in the SON it represented 36% of OT-IR and 16% AVP-IR. Catecholaminergic cell groups in the pons (LC) and medulla (VLM, NTS) were also activated by proximal colon distension. Of the TH-IR neurons in VLM and NTS, 74% and 42% respectively were double labeled. These results indicate that colon distension stimulates OT-, AVP- and CRF-containing hypothalamic neurons, likely involved in the integration of colonic sensory information to modulate autonomic outflow and pain-related responses. Activation of medullary catecholaminergic centers might reflect the afferent and efferent limbs of the functional responses associated to visceral pain.

Topics: Animals; Autonomic Pathways; Brain; Brain Mapping; Catecholamines; Colon; Corticotropin-Releasing Hormone; Hypothalamus; Immunohistochemistry; Male; Neurons; Neuropeptides; Oxytocin; Pain; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Reticular Formation; Rhombencephalon; Vasopressins; Visceral Afferents

Topics: Animals; Carbon Dioxide; Endocrinology; Euthanasia; Hypnotics and Sedatives; Male; Oxytocin; Pain; Rats; Vasopressins; Veterinary Medicine

Nociceptive stimulation elicits neuroendocrine responses such as arginine vasopressin (AVP) release as well as activation of the hypothalamo-pituitary-adrenal axis. We have generated novel transgenic rats expressing an AVP-enhanced green fluorescent protein (eGFP) fusion gene, and we examined the effects of nociceptive stimulation on transgene expression in the hypothalamus after subcutaneous injection of saline or formalin into the bilateral hindpaws in these rats. We have assessed (1) AVP levels in plasma and the changes of eGFP mRNA and AVP heteronuclear RNA (hnRNA) in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) using in situ hybridization histochemistry, (2) gene expression changes in distinct magnocellular and parvocellular divisions of the PVN, (3) eGFP fluorescence in the SON, the PVN, the median eminence (ME), and the posterior pituitary gland (PP). Plasma AVP levels were significantly increased 15 min after formalin injection. In the same time period, the AVP hnRNA levels in the PVN were increased, especially in the parvocellular division of the PVN in formalin-injected rats. In the same region, eGFP mRNA levels after formalin injection were also significantly increased to a much greater extent than those of AVP hnRNA. The eGFP fluorescence in the SON, the PVN, the ME, and the PP was markedly increased in formalin-injected rats and especially increased in the parvocellular divisions of the PVN. Together, our results demonstrate robust and rapid changes in the expression of the AVP-eGFP transgene in the rat hypothalamus after acute nociceptive stimulation.

Topics: Afferent Pathways; Animals; Corticotropin-Releasing Hormone; Formaldehyde; Gene Expression Regulation; Green Fluorescent Proteins; Male; Osmolar Concentration; Pain; Paraventricular Hypothalamic Nucleus; Plasma; Proto-Oncogene Proteins c-fos; Radioimmunoassay; Rats; Rats, Transgenic; Rats, Wistar; RNA, Messenger; Sodium; Supraoptic Nucleus; Vasopressins

We reported a 92-year-old woman with hyponatremia (117 mmol/l) occurring three days after the introduction of tramadol. Diagnosis of inappropriate antidiuretic hormone secretion was based on blood and urinary analysis and dosage of antidiuretic hormone. Natremia became normal after tramadol cessation and fluid restriction. Natremia must be measured when neurological abnormality occurs with tramadol treatment.

Topics: Aged, 80 and over; Analgesics, Opioid; Female; Humans; Hyponatremia; Muscle, Skeletal; Pain; Tramadol; Vasopressins

A 71-year old man with failed back syndrome was admitted to hospital with oliguria that had occurred 4 days after his dose of paroxetine had been increased to 40 mg x day(-1). Laboratory data on admission revealed hyponatremia (124 mmol x l(-1)), low serum osmolarity (267 mOsm x l(-1)) with a normal level of serum antidiuretic hormone (1.7 pg x ml(-1)), and concentrated urine (430 mOsm x l(-1)). He was diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone, associated with paroxetine; this drug was discontinued immediately after admission. The hyponatremia was treated with saline infusion, water restriction, and furosemide; serum sodium level returned to normal on hospital day 5. Paroxetine is being increasingly used for depression and chronic pain management because of its favorable side-effect profile; however, we should be alert to hyponatremia in patients on paroxetine by carrying out periodic monitoring of serum electrolytes, especially in elderly patients.

Topics: Aged; Antidepressive Agents, Second-Generation; Chronic Disease; Depressive Disorder; Electrolytes; Humans; Hyponatremia; Inappropriate ADH Syndrome; Intervertebral Disc Displacement; Male; Pain; Paroxetine; Sodium; Spinal Stenosis; Vasopressins

Recently, there has been a growing interest in long-term consequences of neonatal pain because modern neonatal intensive care units routinely employ procedures that cause considerable pain and may be followed by local inflammation and hyperalgesia lasting for several hours or even days. To address this question, we developed a rat model of short lasting (<2 days) early local inflammatory insult produced by a single injection of 0.25% carrageenan (CAR) into the plantar surface of a hindpaw. Previously, we demonstrated that rats receiving this treatment within the first week after birth grow into adults with a global reduction in responsiveness to acute pain. Here, we report that these animals also manifest a low anxiety trait associated with reduced emotional responsiveness to stress. This conclusion is based in the following observations: (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in the forced swim test, these rats exhibit behavioral characteristics associated with stronger ability for stress coping; and (c) these animals have reduced basal and stress-induced plasma levels of such stress-related neuroendocrine markers as corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In addition, we used DNA microarray and real-time reverse-transcriptase polymerase chain reaction to profile long-term changes in gene expression in the midbrain periaqueductal gray (PAG; a region involved in both stress and pain modulation) in our animal model. Among the affected genes, serotonergic receptors were particularly well represented. Specifically, we detected increase in the expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of these receptors are known to be involved in the anxiolytic and analgesic activity of the PAG. Finally, to determine whether neonatal inflammatory insult induces elevation in maternal care, which may play a role in generating long-term behavioral alterations seen in our model, we examined maternal behavior for 3 days following CAR injection. Indeed, we observed a substantial increase in maternal attention to the pups at the time of inflammation, but this increase was not without its cost: a period of significant maternal neglect afterward.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; Animals; Animals, Newborn; Behavior, Animal; Brain Chemistry; Carrageenan; Carrier Proteins; Corticotropin-Releasing Hormone; Disease Models, Animal; Edema; Enzyme-Linked Immunosorbent Assay; Female; Inflammation; Male; Maternal Behavior; Maze Learning; Oligonucleotide Array Sequence Analysis; Pain; Pain Measurement; Periaqueductal Gray; Phosphoproteins; Rats; Receptors, Serotonin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stress, Psychological; Swimming; Time Factors; Vasopressins

To investigate the role of the hormone vasopressin (VP) in mediating the response of an organism to food restriction stress-induced analgesia, tail flick latencies and scored qualitative behavioral responses were recorded in VP-containing (LE) rats and VP-deficient (DI) rats. These variables were measured under nonstressed (ad lib) and stressed (food restriction) conditions. In the ad lib condition, DI and LE rats had a similar tail flick latency and scored qualitative behavioral response to the stimulus eliciting the tail flick. During the food restriction condition, however, LE animals developed significant food restriction stress-induced analgesia, as measured by tail flick latency. On the other hand, DI animals did not develop significant analgesia. In addition, DI animals exhibited a significantly greater scored qualitative behavioral response to the stimulus eliciting the tail flick than LE animals. These results demonstrate that VP plays an important role in the regulation of food restriction stress-induced analgesia, as well as the scored qualitative behavioral response elicited by the tail flick stimulus.

Topics: Analgesia; Animals; Food Deprivation; Male; Neurosecretory Systems; Pain; Pain Measurement; Rats; Rats, Brattleboro; Stress, Physiological; Vasopressins

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.

Topics: Animals; Axonal Transport; Dihydrolipoamide Dehydrogenase; Escherichia coli; Fluorescent Dyes; Genes, fos; Immunohistochemistry; In Situ Hybridization; Lipopolysaccharides; Male; Neurons; Nitric Oxide Synthase; Oxytocin; Pain; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Restraint, Physical; Saline Solution, Hypertonic; Spinal Cord; Stilbamidines; Stress, Physiological; Stress, Psychological; Supraoptic Nucleus; Time Factors; Vasopressins

Noxious somatic stimuli elicit vasopressin secretion, an effect thought to result from activation of a facilitatory input from A1 catecholamine cells of the medulla oblongata. To better characterize the A1 cell response and effects on other neuroendocrine A1 projection targets, particularly within the paraventricular nucleus, we have now mapped c-fos expression in neurochemically identified catecholamine and neurosecretory cells following a noxious somatic stimulus. Unilateral hind paw pinch significantly increased c-fos expression in contralateral A1 cells whereas other brainstem catecholamine cell groups were unaffected. Expression of c-fos was also increased in the supraoptic nucleus, this effect being more pronounced for vasopressin than oxytocin neurosecretory cells and, as with A1 cells, primarily on the side contralateral to the stimulated paw. In contrast, the increase in the paraventricular nucleus was greater in oxytocin rather than in vasopressin cells. Additionally there was a significant rise in c-fos expression in medial parvocellular paraventricular nucleus cells of noxiously stimulated animals. Notably, the majority of tuberoinfundibular corticotropin-releasing factor cells are located in this medial parvocellular zone. These results are consistent with and expand on those previously reported from electrophysiological and anatomical studies. The finding of differing neurosecretory cell responses between supraoptic and paraventricular nuclei has interesting implications with regard to the afferent control of neurosecretory cell activity. For example, the substantially greater activation of supraoptic versus paraventricular nucleus vasopressin cells, despite being innervated by the same medullary noradrenergic cell group, raises the possibility of a differential input or differences in responsiveness. Furthermore, the activation of paraventricular nucleus parvocellular cells is consistent with suggestions that the A1 cell group provides an excitatory input to this population.

Topics: Animals; Brain Stem; Catecholamines; Gene Expression; Genes, fos; Histocytochemistry; Hypothalamus; Male; Neurosecretory Systems; Pain; Paraventricular Hypothalamic Nucleus; Physical Stimulation; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Supraoptic Nucleus; Vasopressins

The discovery of immediate early genes (IEG) has provided neuroscientists with a new functional mapping technique. Labelling of neural tissue for the protein product of IEG provides an activity map with single-cell resolution. When combined with labelling for the chemical identity of the neuron, this provides a powerful tool for the investigation of specific cell populations along a neuraxis. Here we describe in detail a method which allows simultaneous bright-field visualization of neurochemically identified cells displaying increased IEG expression. This technique is evaluated in tissue from rats subjected to stimuli known to induce the expression of the IEG c-fos in various medullary catecholaminergic and hypothalamic neurosecretory cell groups. A 2-colour immunoperoxidase technique was used to visualize Fos, the nuclear protein product of c-fos, and the cytoplasmic antigens tyrosine hydroxylase (TH), phenylethanolamine N-methyl transferase (PNMT), oxytocin (OT) and vasopressin (VP). This involved simultaneous application of primary antibodies raised in different species followed by sequential application of appropriate biotinylated secondary antibodies and the avidin-biotin-peroxidase technique. Fos was visualized with nickel-intensified diaminobenzidine (Ni-DAB) in the first sequence while TH, PNMT, OT or VP were visualized with DAB alone, resulting in readily distinguishable black and amber reaction products, respectively. This dual immunoperoxidase technique is time saving compared to techniques using sequential application of primary antibodies and avoids the disadvantages associated with fluorescence techniques.

Topics: Animals; Biomarkers; Gene Expression Regulation; Hypothalamus; Immunoenzyme Techniques; Male; Medulla Oblongata; Nerve Tissue Proteins; Neurons; Osmotic Pressure; Oxytocin; Pain; Phenylethanolamine N-Methyltransferase; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Reserpine; Tyrosine 3-Monooxygenase; Vasopressins

Plasma cortisol, prolactin and vasopressin concentrations were measured by radioimmunoassay in blood samples from control and lame sheep. The lame sheep were all suffering from naturally occurring clinical cases of footrot and showed all the behavioural characteristics of chronic pain; they were scored for impairment of gait and pathology of the foot and divided into mild and severely lame groups. The severely lame sheep had increased plasma prolactin and decreased plasma cortisol concentrations. Plasma vasopressin was variable and showed no consistent changes with lameness. The relationships between plasma cortisol, prolactin and vasopressin may be a useful index in the assessment of animals experiencing chronic pain, when taken in conjunction with other measurements.

Topics: Animals; Chronic Disease; Female; Foot Rot; Hydrocortisone; Lameness, Animal; Pain; Prolactin; Radioimmunoassay; Sheep; Sheep Diseases; Vasopressins

This study was undertaken to evaluate the analgesic effect of paraventricular nucleus (PVN) stimulation with tail stimulation-vocalization test. The mechanism of this analgesia was analysed with nuclear lesion and microinjection technique. The main results were as follows: (1) Electrical stimulation of the PVN could significantly enhance the pain threshold and increase the content of AVP in brainstem measured by radioimmunoassay. (2) Solitary tract nucleus (STN) lesion could eliminate the analgesic effect induced by PVN stimulation. (3) Intranuclear microinjection of AVP-antagonist and AVP-antiserum into the STN could block the analgesic effect of PVN stimulation. (4) Intranuclear microinjection of AVP into the STN could mimick the analgesic effect similar to that of PVN stimulation. These results suggest that electrical stimulation of the PVN could produce an analgesic effect. This effect might be mediated by the activation of VP-ergic neurons in PVN and upon releasing VP from the descending fibers, the activities of neurons in the STN are influenced.

Topics: Animals; Electric Stimulation; Male; Medulla Oblongata; Microinjections; Nociceptors; Pain; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Sensory Thresholds; Vasopressins

The effects of intrathecal (i.t.) vasopressin (VP) on nociception were quantitatively tested in rats using 4 pain tests: tail flick, tail shock vocalization, hot plate, and formalin. In addition, motor effects of VP were examined qualitatively. I.t. VP produced a prolonged antinociception lasting at least 40 min on the tail flick (2.5 and 25 ng) and formalin (25 ng) tests, and a brief antinociception lasting less than 20 min on the tail shock (25 ng) and hot plate (25 ng) tests. Those rats not responding to the pain tests showed no signs of perceiving the pain stimulus, such as orientation to the stimulus or vocalization. In addition, i.t. VP produced scratching bouts (2.5 and 25 ng) and suppressed hindbody motor function (25 ng). The motor inhibitory effects of VP, although severe in some rats, were brief, lasting less than 15 min. In conclusion, i.t. VP produces antinociception in addition to its motor effects, and these properties appear to be due to separate mechanisms.

Topics: Animals; Dose-Response Relationship, Drug; Hot Temperature; Injections, Spinal; Locomotion; Male; Nociceptors; Pain; Rats; Rats, Inbred Strains; Reaction Time; Vasopressins

Effects of electric foot shocks (FSs) on plasma immunoreactive vasopressin (ir-VP) were studied in relation to FS frequency in conscious and anesthetized rats under a hypertonic condition. The plasma ir-VP level was significantly lower after low-frequency FSs (0.05-0.2 Hz) but significantly higher after high-frequency FSs (5 Hz) in conscious rats. Plasma ir-VP was significantly higher in anesthetized rats after FSs at frequencies of either 0.2 or 50 Hz compared to unshocked control rats. These data support the hypothesis that FSs activate two distinct neural mechanisms: one potentiates and the other suppresses VP secretion.

Topics: Anesthesia; Animals; Electroshock; Foot; Male; Neurons, Afferent; Pain; Rats; Rats, Inbred Strains; Time Factors; Vasopressins

Whether plasma vasopressin (VP) mediates footshock-induced analgesia was examined in conscious rats. Footshocks significantly increased threshold temperature of tail flick and plasma VP as reported previously. Intravenous VP increased the threshold only in doses that are considered to elevate plasma VP to a level more than 500 times higher than that after footshocks. In addition, posterior pituitary stimulation increased plasma VP to a level ten times higher than that after footshocks but did not significantly change the threshold. It is therefore highly likely that plasma VP is not involved in footshock-induced analgesia.

Topics: Analgesia; Animals; Electroshock; Male; Pain; Rats; Rats, Inbred Strains; Vasopressins

In an electrophysiological study designed to examine the negative feedback effects of glucocorticoid hormones, we have recorded the electrical activity of 147 neurones in the paraventricular nucleus of the rat hypothalamus. 37 (25%) of the neurones were antidromically identified as projecting to the median eminence and were located at a mean depth of 2.35 +/- 0.08 mm from the base of the brain, corresponding with the corticotropin-releasing factor-rich region of the nucleus. The mean firing rate of the identified cells was 4.7 +/- 0.6 Hz which was not significantly different from that of adjacent, unidentified cells (5.6 +/- 0.6 Hz). Most (17/18, 94%) of these cells tested responded to painful somatosensory stimuli and 26 (74%) of the identified cells were inhibited by iontophoretic application of corticosterone and/or hydrocortisone, whereas only one cell was excited and 8 unaffected. Of the identified cells, only 18 (20%) were inhibited, 36 (41%) were excited and 34 (39%) were non-responsive. The proportion of inhibitory responses was thus greater for the identified cells (P less than 0.005; chi 2-test). For the identified cells, whose spontaneous activity was unaffected by glucocorticoid application, glutamate-evoked responses could usually be depressed by the application. The time course of all responses usually showed an immediate onset, increasing in magnitude and continuing for extended periods following cessation of iontophoresis. Electrophysiologically identified magnocellular neurones were also tested and the majority (7/12, 58%) of vasopressin-secreting neurons were also found to be inhibited, whilst all (8/8, 100%) of the oxytocin-secreting neurones were excited by the glucocorticoid application. These results may represent an electrophysiological correlate of the negative feedback control of adrenocortical secretion and are discussed within this context.

Topics: Action Potentials; Animals; Corticosterone; Glucocorticoids; Hydrocortisone; Iontophoresis; Male; Neural Inhibition; Oxytocin; Pain; Rats; Vasopressins

Topics: Animals; Arousal; Avoidance Learning; Behavior, Animal; Brain; Drug Tolerance; Female; Maternal Behavior; Mental Recall; Opioid-Related Disorders; Oxytocin; Pain; Pituitary Gland, Posterior; Rats; Spinal Cord; Synaptic Transmission; Vasopressins

The effects of i.p. injected hypertonic NaCl and polyethylene glycol on the magnitude of increase in plasma vasopressin after footshocks were studied in male rats, to determine whether hypovolemia and body fluid osmolality interact with noxious stimuli on vasopressin secretion. Present data have demonstrated that non-osmotic hypovolemia but not body fluid hyperosmolarity interact significantly and synergistically with footshocks to potentiate vasopressin secretion.

Topics: Animals; Blood Volume; Electroshock; Hemoglobins; Male; Osmolar Concentration; Pain; Pituitary Gland, Posterior; Polyethylene Glycols; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Vasopressins

The existence of a wide variety of neuropeptides within the spinal cord dorsal horn raises the question of their possible roles in sensory processing. The present series of behavioral experiments examined the effects of intrathecal (IT) administration of two such neuropeptides, thyrotropin-releasing hormone (TRH) and vasopressin (VAS), on pain sensitivity and antinociception. TRH exerted no marked effect on basal pain sensitivity over the dose range examined (0.25 ng-2.5 micrograms). However, a U-shaped dose-response effect on morphine antinociception (3 micrograms, IT) was observed, wherein potent attenuation, moderate attenuation, or enhancement of morphine-induced antinociception was observed following the various doses tested. In contrast, VAS produced non-opiate antinociception at the highest doses tested (25 ng and 250 ng) and none of the VAS doses (0.25 ng-250 ng) appeared to interact with IT morphine (3 micrograms) antinociception. Lastly, IT TRH was not observed to interact with IT VAS antinociception. These data provide evidence that these neuropeptides exert strikingly different effects on pain sensitivity and opiate antinociception, and provide initial evidence that TRH may be included in the growing list of neuropeptides that can act like endogenous opiate antagonists within the central nervous system.

Topics: Analgesia; Animals; Injections, Spinal; Male; Morphine; Nerve Tissue Proteins; Nociceptors; Pain; Rats; Rats, Inbred Strains; Spinal Cord; Thyrotropin-Releasing Hormone; Vasopressins

Inoculation of rats at the tail-base with Mycobacterium led to arthritic swelling and inflammation of all four limbs. Immunoreactive (ir)-dynorphin (DYN) increased in anterior but not neurointermediate pituitary. In the brain, only thalamus showed a rise and, in spinal cord, a large elevation was seen. Ir-vasopressin (VP) was not affected in these tissues but increased in midbrain. These effects might reflect a role of DYN in the control of chronic pain. In addition, they support a differential modulation of DYN as compared to VP extrinsic to the hypothalamic-neurohypophyseal axis.

Topics: Animals; Central Nervous System; Chronic Disease; Dynorphins; Mesencephalon; Pain; Pituitary Gland, Anterior; Rats; Spinal Cord; Thalamus; Vasopressins

Acute exposure to either prolonged intermittent foot shock (PIFS) or brief continuous foot shock, (BCFS) decreases the sensitivity of rats to noxious stimuli, but differ in their mechanisms of actions. Since the peptide vasopressin (VP) has been implicated in analgesic and stress-related processes, the present study examined whether antagonism of central VP receptors with dPTyr(Me)AVP would alter the analgesic responses following PIFS or BCFS. While intracerebroventricular administration of dPTyr(Me)AVP, a V1 receptor antagonist, significantly attenuated the analgesic response to PIFS, it potentiated the analgesic response to BCFS. It should be noted that the form of PIFS employed in the present study was not blocked by naloxone. These results are discussed in terms of multiple forms of pain-inhibitory systems that may utilize collateral inhibition as a means of providing selective activation.

Topics: Analgesia; Animals; Arginine Vasopressin; Female; Foot; Hot Temperature; Injections, Intraventricular; Nociceptors; Pain; Rats; Rats, Inbred Strains; Reaction Time; Receptors, Cell Surface; Vasopressins

Rats inoculated in the tail-base with killed Mycobacterium butyricum developed an arthritic swelling and inflammation of the limbs accompanied by a hyperalgesia to noxious pressure applied thereto. These changes were maximal at 3 weeks and had subsided by 10 weeks post-inoculation. At 3 weeks, arthritic rats manifested an elevation in levels of immunoreactive (ir)-vasopressin (VP) but not ir-oxytocin (OT) in the midbrain. In contrast, ir-OT was increased in the medulla-pons while ir-VP was unaltered therein. These changes had disappeared by 10 weeks. No other brain region displayed changes. Thus, chronic arthritis is associated with selective and reversible effects upon discrete brain pools of ir-VP and ir-OT. The data clearly demonstrate that pools of ir-VP and ir-OT can be modulated independently of each other in particular brain tissues. Whether the changes are produced by, or reflect a functional response to, the pain rather than other characteristic of the arthritis, remains to be determined.

Topics: Animals; Arthritis; Arthritis, Experimental; Brain Chemistry; Chronic Disease; Male; Oxytocin; Pain; Rats; Rats, Inbred Strains; Stress, Physiological; Vasopressins

Experiments were carried out to investigate whether vasopressin is involved in stress-induced analgesia. Intraperitoneal injection of hypertonic saline caused a significant and dose-related increase in the latency to the tail-flick response of the rat to noxious heat and was used as a stimulus for stress-induced analgesia. Neither the pituitary nor opioid peptides appeared to be involved, since the response occurred in hypophysectomized rats and was not reduced by the opiate antagonist naloxone. Furthermore hypertonic-saline analgesia was clearly potentiated in hypophysectomized rats in comparison to sham-operated controls. Hypertonic-saline analgesia was also observed in vasopressin-deficient (homozygous Brattleboro) rats similar in both magnitude and duration to that in normal rats of the same strain (Long Evans). It was concluded that vasopressin was not involved in stress-induced analgesia evoked by hypertonic saline.

Topics: Animals; Diabetes Insipidus; Homozygote; Male; Pain; Rats; Rats, Brattleboro; Saline Solution, Hypertonic; Sodium Chloride; Stress, Physiological; Vasopressins

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

The purpose of this note is to show that vasopressin might be involved in the hypoalgesia of the spontaneously hypertensive rat. This proposal rests upon published data.

Topics: Animals; Hypertension; Pain; Rats; Rats, Inbred Strains; Sensory Thresholds; Vasopressins

Lesions of the hypothalamic paraventricular nucleus depleted immunoreactive (ir)-vasopressin (VP) and -oxytocin (OT) from rat spinal cord but failed to modify nociceptive thresholds. Further, intrathecal introduction of VP and OT into the cord failed either to influence nociceptive thresholds or to modify the antinociceptive action of morphine. However, doses of VP as low as 20 ng caused, in contrast to OT, a hind-limb muscular flaccidity and respiratory disturbances. Rats suffering from chronic arthritis did not, finally, reveal any alterations in levels or ir-VP or ir-OT in the spinal cord. Is is concluded that spinal pools of VP and OT are derived from the paraventricular nucleus and do not play a major role in nociceptive processes in the spinal cord. A role of spinal VP in motor and, possibly autonomic control is, nevertheless, indicated.

Topics: Animals; Arthritis, Experimental; Chronic Disease; Male; Morphine; Oxytocin; Pain; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Sensory Thresholds; Spinal Cord; Vasopressins

Both vasopressin and PGF2 alpha are effective uterine stimulants in the non-pregnant human uterus, especially around the onset of menstruation. In order to clarify the relationship of these hormones to menstrual pain, plasma concentrations of vasopressin and two prostaglandin metabolites (15-keto-13,14-dihydro-PGF2 alpha and 11-ketotetranor PGF metabolites) were measured in serial blood samples taken premenstrually and during menstruation. Five women with premenstrual pain gave 7-9 blood samples at intervals of 30 minutes on the day preceding the onset of menstruation. From 5 women with severe primary dysmenorrhea a corresponding series of blood samples were taken during the first day of menstruation. Two groups of 5 women with no symptoms served as controls, either premenstrually or during menstruation. In the women with premenstrual pain the vasopressin concentrations were significantly higher than in the corresponding control group. Even higher and markedly fluctuating vasopressin levels were found in the women with dysmenorrhea who, in general, had more intense pain than the women with premenstrual symptoms. In the group with dysmenorrhea there was also a significant rise in plasma concentration of the PG metabolites. No such increase was seen in the group with premenstrual pain. It is concluded that the pathophysiology of premenstrual pain could imply increased vasopressin secretion. The more severe pain in primary dysmenorrhea seems to be the result of a combined effect of vasopressin and PGF2 alpha.

Topics: Adolescent; Adult; Dinoprost; Dysmenorrhea; Estradiol; Female; Humans; Osmolar Concentration; Pain; Premenstrual Syndrome; Progesterone; Prostaglandins F; Vasopressins

Topics: Adult; Aged; Female; Humans; Indomethacin; Male; Middle Aged; Osmolar Concentration; Pain; Ureteral Calculi; Vasopressins; Water-Electrolyte Balance

We have studied plasma and cerebrospinal fluid vasopressin (CSF-AVP) and osmolality in 28 patients with cervical or lumbar pain syndromes (control patients), 11 patients with normal pressure hydrocephalus (NPH) and in 5 patients with benign intracranial hypertension (BIH). Vasopressin concentration in lumbar CSF to a high extent reflected the actual ventricular CSF-AVP concentration. In all groups CSF-AVP was lower than plasma AVP. Mean CSF-AVP in the control group was 1.3 pg/ml +/- 0.1 (SEM). In the NPH patients, who all suffered from severe dementia, CSF-AVP level was not different from that found in the control group (1.4 pg/ml +/- 0.2). In contrast to the findings in the two other groups CSF osmolality in BIH patients was higher than plasma osmolality (P less than 0.0). CSF-AVP in the BIH patients, characterized by an elevated intracranial pressure (ICP), was higher than in the control group (2.7 pg/ml +/- 0.4, P less than 0.001).

Topics: Adult; Aged; Cervical Vertebrae; Female; Humans; Hydrocephalus; Hydrocephalus, Normal Pressure; Lumbar Vertebrae; Male; Middle Aged; Osmolar Concentration; Pain; Pseudotumor Cerebri; Syndrome; Vasopressins

The effect of pain on plasma AVP concentration in man has previously been studied only during major surgery with general anaesthesia. Plasma AVP concentration (pAVP) and plasma osmolality (pOsm) were measured in thirty-six patients seen in a surgical emergency department complaining of pain and in fifty-one control subjects. No significant difference in pOsm was found, but pAVP was significantly higher in the emergency room patients in pain (M +/- SEM = 4.94 +/- 0.98 pmol/1 compared to 2.31 +/- 0.32 pmol/1 in control subjects, P less than 0.01). In the control subjects, age was found to have a low but significant inverse correlation with pAVP (r = 0.37, P less than 0.01). Chronic smoking was associated with significant elevation of pAVP (3.81 +/- 0.99 pmol/1 in smokers vs. 1.89 +/- 0.28 pmol/1 in non-smokers, P less than 0.02). Neither smoking nor age could account for the difference in pAVP between the pain and control groups. Thus, pain is a non-osmolar factor capable of elevating AVP in conscious man.

Topics: Adolescent; Adult; Age Factors; Arginine Vasopressin; Female; Humans; Male; Middle Aged; Osmolar Concentration; Pain; Smoking; Vasopressins

Topics: Animals; Behavior; Body Temperature Regulation; Brain Stem; Cerebral Ventricles; Cerebrospinal Fluid; Circadian Rhythm; Electrophysiology; Female; Glucose; Hemodynamics; Hypothalamo-Hypophyseal System; Hypothalamus; Lactation; Limbic System; Lipid Metabolism; Neural Inhibition; Neural Pathways; Oxytocin; Pain; Pregnancy; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Acetylcholine; Action Potentials; Adenosine; Adenosine Triphosphate; Angiotensin II; Animals; Blood Pressure; Drug Synergism; Ear; Eledoisin; Epinephrine; Female; Histamine; In Vitro Techniques; Male; Oxytocin; Pain; Peptides; Potassium Chloride; Prostaglandins; Rabbits; Respiration; Sensory Receptor Cells; Serotonin; Substance P; Time Factors; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins; Venous Pressure

Topics: Action Potentials; Animals; Arousal; Chemoreceptor Cells; Electroencephalography; Haplorhini; Hypothalamus; Neurons; Osmolar Concentration; Pain; Pituitary Gland, Posterior; Sleep; Vasopressins; Wakefulness; Water-Electrolyte Balance

Topics: Angiotensin II; Animals; Arecoline; Bradykinin; Carbachol; Catecholamines; Dogs; Dopamine; Epinephrine; Injections, Intra-Arterial; Injections, Intraperitoneal; Methacholine Compounds; Norepinephrine; Oxytocin; Pain; Parasympathomimetics; Peptides; Reaction Time; Sensory Receptor Cells; Splenic Artery; Vasopressins

Topics: Adult; Animals; Arousal; Biological Assay; Blood Pressure; Cold Temperature; Epinephrine; Heart Rate; Humans; Male; Norepinephrine; Pain; Rats; Stress, Physiological; Stress, Psychological; Urine; Vasopressins

Topics: Anesthesia, Dental; Anesthetics, Local; Dental Pulp Diseases; Drug Synergism; Epinephrine; Felypressin; Injections; Lidocaine; Mepivacaine; Norepinephrine; Pain; Prilocaine; Sympathomimetics; Vasopressins

Topics: Animals; Diuresis; Dogs; Hemorrhage; Monitoring, Physiologic; Pain; Vasopressins; Wounds and Injuries

Topics: Anesthesia; Animals; Diuresis; Ethanol; Hemorrhage; Hypophysectomy; Male; Osmosis; Pain; Rats; Vasopressins

Topics: Animals; Dogs; Electric Stimulation; Female; Pain; Vasopressins

Topics: Chest Pain; Diagnosis, Differential; Humans; Pain; Thorax; Vasopressins