beta-endorphin and Pain--Intractable

The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma β-endorphin levels in cancer patients.. A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma β-endorphin levels were measured by radioimmunoassay.. With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma β-endorphin levels. After the treatment, plasma β-endorphin level in group B was 62.4±13.5 pg/ml, which was higher than that in group A (45.8±11.2 pg/ml) (p<0.05).. Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma β-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Topics: Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; beta-Endorphin; Drug Synergism; Drug Therapy, Combination; Female; Flurbiprofen; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Pain, Intractable; Prognosis; Quality of Life; Radioimmunoassay

Topics: Analgesia; beta-Endorphin; Humans; Neoplasms; Pain, Intractable; Pain, Postoperative

Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF).. Cross-sectional, comparative, observational study.. Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N = 15) and healthy controls (N = 19) were included.. Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit.. We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66 ± 11 pcg/mL) compared with healthy controls (115 ± 14 pcg/mL) (P = 0.017). Substance P levels in the CSF did not differ (20 ± 2 pcg/mL, 26 ± 2, P = 0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs  = 0.725, P < 0.001 vs. rs  = 0.574, P = 0.032).. Patients with chronic neuropathic pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers.

Topics: Adult; Analgesics; beta-Endorphin; Biomarkers; Chronic Pain; Clinical Trials as Topic; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Neuralgia; Pain, Intractable; Pain, Postoperative; Substance P

The authors systematically studied the release of the endogenous opioid peptides beta-endorphin and methionine (met)-enkephalin into the cerebrospinal fluid (CSF) during deep brain stimulation in patients suffering from otherwise intractable chronic pain. Nine patients were included in the study; six had stimulation electrodes placed in both the periventricular gray matter (PVG) and the thalamic nucleus ventralis posterolateralis (VLP) and three in the PVG only. Immunoreactivity of beta-endorphin and met-enkephalin (beta-EPir and MEir, respectively) was measured by radioimmunoassays in ventricular and lumbar CSF samples obtained before, during, and after stimulation. Prestimulation concentrations of beta-EPir and MEir were lower in ventricular than in lumbar CSF (6.6 +/- 0.5 vs. 13.7 +/- 1.0 pmol/liter, p = 0.0001, for beta-EPir; 33.6 +/- 5.1 vs. 48.3 +/- 3.2 pmol/liter, p < 0.05, for MEir). Ventricular CSF concentrations of both beta-EPir and MEir increased significantly during PVG stimulation, whereas VPL stimulation was without effect. No changes were seen in lumbar CSF levels of the peptides during stimulation in either site. A significant inverse relationship was found between the "during:before stimulation" ratios of visual analog scale ratings and beta-EPir levels during PVG stimulation. The beta-EPir and MEir concentration during:before stimulation ratios were positively correlated, whereas no correlation was present in prestimulation samples from ventricular or lumbar CSF. High-performance liquid chromatography of ventricular CSF pools obtained during PVG stimulation revealed that major portions of beta-EPir and MEir eluted as synthetic beta-endorphin and met-enkephalin, respectively, thus documenting the release of beta-endorphin and met-enkephalin into ventricular CSF during PVG stimulation. The finding of a direct relationship between beta-EPir release and pain alleviation may suggest a role for beta-endorphin in the analgesic mechanism of PVG stimulation.

Topics: Adult; Aged; beta-Endorphin; Chronic Disease; Electric Stimulation Therapy; Electrodes, Implanted; Enkephalin, Methionine; Evoked Potentials; Female; Humans; Male; Middle Aged; Pain Measurement; Pain, Intractable; Periaqueductal Gray; Thalamic Nuclei

Effects of dorsal root entry zone lesions (DREZLs) on cerebrospinal fluid (CSF) and plasma concentrations of neuropeptides, catecholamines, and cyclic nucleotides were studied in 9 patients with intractable chronic pain. Contents of beta-endorphin-like-material in CSF decreased in all patients 12-17 days following DREZLs during which complete to good pain relief was achieved. Contents of beta-endorphin-like-material in CSF increased again about one month after DREZLs in two and remained unchanged in one of three patients tested, who complained of partial reappearance of pain. Contents of beta-endorphin-like-materials in plasma showed no significant changes after DREZLs. Substance P, noradrenaline, adrenaline, and cyclic nucleotide levels in both CSF and plasma were variable among the subjects and did not change significantly following the operations. Thus, the results suggest that production of beta-endorphin-like-material in the central nervous system is decreased by DREZL, though the increase in its turn-over might not be neglected. The mechanisms of the decrease in contents of beta-endorphin-like-material in CSF after DREZLs were discussed in terms of our current knowledge of pain and pain inhibitory systems.

Topics: Adult; beta-Endorphin; Blood-Brain Barrier; Catecholamines; Cyclic AMP; Cyclic GMP; Female; Ganglia, Spinal; Humans; Male; Middle Aged; Neuralgia; Neuropeptides; Pain Measurement; Pain, Intractable; Substance P

Concentrations of beta-endorphin in the cerebrospinal fluid were measured in 21 painless subjects and 37 patients with chronic pain. Statistical analysis of the results showed no significant difference between the two groups. This lack of correlation between beta-endorphin concentrations in the CSF and the presence of chronic pain highlights the difficulties and limitations encountered when trying to determine the role of endogenous opioid systems with this method.

Topics: beta-Endorphin; Chronic Disease; Humans; Pain, Intractable; Radioimmunoassay; Reproducibility of Results

The effect of the combined preparation analgeton and its components--analgin (metamizol, noramidopyrindimethansulfonate) and aminton (2-amino-4-methyl-pyridinphosphate) was studied on the release of beta-endorphin and its influence on chronic hyperalgesia. Experiments were carried out in vivo and in vitro on white rats and it was established that analgin, aminton and analgeton stimulated the release of beta-endorphin, affecting various regulatory levels. Analgeton in contrast to analgin showed longer analgetic effect in animals with chronic hyperalgesia (adjuvant arthritis of white rats). Possibilities for pharmacological control of chronic pain by influencing the levels of endogenous opioids are discussed.

Topics: Aminopyrine; Animals; beta-Endorphin; Chronic Disease; Dipyrone; Drug Combinations; Hyperalgesia; Hyperesthesia; Male; Pain, Intractable; Picolines; Rats; Rats, Inbred Strains

Topics: beta-Endorphin; Dose-Response Relationship, Drug; Drug Evaluation; Endorphins; Humans; Hydroxyindoleacetic Acid; Injections, Spinal; Morphine; Neoplasms; Pain Measurement; Pain, Intractable

Topics: beta-Endorphin; Endorphins; Female; Humans; Injections, Spinal; Middle Aged; Neoplasms; Pain, Intractable

We studied the cerebrospinal fluid (CSF) and plasma concentration-time profiles of morphine, methadone, and beta-endorphin after lumbar epidural or intrathecal injection in 17 patients with cancer. After epidural injection, all three drugs reached peak levels in lumbar CSF within 34 minutes that were 50 to 1300 times higher than free drug concentrations in plasma. The rate of decline of CSF levels correlated with drug lipid solubility (methadone [t1/2 = 73 minutes] greater than morphine [126 minutes] greater than beta-endorphin [317 minutes]). Plasma levels were comparable with those after intragluteal injection of the same dose. In four patients given intrathecal morphine or methadone, CSF at the C1-2 level contained high levels of morphine as early as 1 hour after injection, but levels of methadone were lower or undetectable. Three of 17 patients reported improved analgesia initially, but none were improved at 2 weeks after chronic therapy. We conclude that analgesia induced by intrathecal or epidural morphine injections is caused by drug acting at both spinal and supraspinal sites. The use of spinal opiates such as morphine is of limited value in patients whose pain is not adequately managed by high systemic doses of morphine-like drugs.

Topics: Adult; Aged; beta-Endorphin; Drug Evaluation; Endorphins; Epidural Space; Female; Half-Life; Humans; Injections, Spinal; Kinetics; Male; Methadone; Middle Aged; Morphine; Neoplasms; Pain, Intractable; Palliative Care

Baseline concentrations of beta-endorphin (beta-EP) and monoamine metabolites (MHPG: 3-methoxy-4-hydroxy-phenylglycol, HVA: homovanillic acid, 5-HIAA: 5-hydroxyindoleacetic acid) in lumbar CSF (LCSF) and ventricular CSF (VCSF) were measured in 18 patients with intractable pain; 10 with deafferented pain and 8 with peripheral pain. Control values were obtained from 37 individuals of various ages. Changes in the concentrations of these substances were determined before and after giving stimulations (2-5 V, 0.2-0.5 msec, 40-50 Hz, 20-sec duration) to 6 patients through electrodes implanted in deep brain structures (DBS; posterior limb of the internal capsule in 5 patients and rostral mesencephalic lemniscus medialis in one patient), and to 2 other patients through electrodes implanted in the spinal dorsal column (DCS). The control value of beta-EP in LCSF was 57.6 +/- 24.7 pg/ml, which was not significantly different from that of VCSF. Great variation in the individual control LCSF beta-EP concentrations was found, but it was not related to differences in age. The mean baseline LCSF beta-EP concentration was significantly higher (p less than 0.05) than the control in the patients with deaffernted pain before stimulation. One of the monoamine-metabolites, MHPG, showed higher level in the patients with peripheral pain (p less than 0.01). The LCSF beta-EP concentration was not affected by deep brain stimulation, but was increased by dorsal column stimulation. In one patient with excellent pain relief by stimulation of the posterior limb of the internal capsule, the LCSF HVA and 5-HIAA concentrations were conspicuously increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; beta-Endorphin; Brain; Child; Electric Stimulation; Endorphins; Female; Ganglia, Spinal; Glycols; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Pain, Intractable

Plasma beta-endorphin levels were found to be significantly lower in patients suffering from chronic pain of malignant etiology than in a control group. After a bilateral stereotactic cryothalamotomy in Centrum Medianum and Parafascicularis nuclei, a good clinical result and a significant increase in plasma beta-endorphin levels were obtained.

Topics: Adult; Aged; beta-Endorphin; Cryosurgery; Endorphins; Female; Humans; Male; Neoplasms; Pain, Intractable; Stereotaxic Techniques; Thalamic Nuclei

Seven cases of chronic pain were treated by intrathecal administration of 30 micrograms of beta-endorphin and dynorphin-(1-13). Compared with saline, both peptides were able to suppress pain for periods up to 4.5 and 7 hours on the average, respectively. No significant side reactions were noticed during the entire investigation.

Topics: Adult; Aged; beta-Endorphin; Cerebral Infarction; Dynorphins; Endorphins; Female; Herpes Zoster; Humans; Injections, Spinal; Male; Middle Aged; Neoplasms; Pain, Intractable; Peptide Fragments; Wounds, Gunshot

D-phenylalanine, bacitracin and puromycin produce long-lasting, naloxone-reversible analgesia in mice. Analgesic potency parallels potency of these compounds as inhibitors of met-enkephalin degradation by mouse brain enzymes. D-phenylalanine potentiates acupuncture analgesia in mice and humans and has been used to ameliorate a variety of human chronic pain conditions.

Topics: Acupuncture Therapy; Analgesia; Analgesics; Animals; Bacitracin; beta-Endorphin; Brain; Drug Synergism; Endorphins; Enkephalin, Methionine; Humans; Kinetics; Mice; Naloxone; Neprilysin; Pain, Intractable; Phenylalanine; Protease Inhibitors; Puromycin; Stereoisomerism

Topics: beta-Endorphin; Brain Chemistry; Endorphins; Female; Humans; Labor, Obstetric; Nociceptors; Pain, Intractable; Pregnancy

Deep brain stimulation (thalamic relay nucleus, periaqueductal gray and internal capsule) was applied to various cases of intractable pain, and the resulting degree of pain reduction and alteration in beta-endorphin immunoreactivity in the cerebrospinal fluid (CSF) were compared. The following results were obtained. (1) The studies on intractable pain revealed that the levels of beta-endorphin immunoreactivity in the CSF were lower than those in the control group. (2) Thalamic relay nucleus stimulation proved effective not only for deafferentiation pain, but also for somatogenic pain. No relationship was, however, noted between pain reduction and the rate of increase of beta-endorphin immunoreactivity in the CSF. (3) The incidence of stimulation tolerance following prolonged stimulation of the thalamic relay nucleus can be reduced to a minimum by administration of L-DOPA. It is concluded that the increase in beta-endorphin in the CSF is not the direct and major cause of pain reduction during treatment by thalamic relay nucleus stimulation. It may be assumed that neuronal facilitation on the monoaminergic descending pain inhibitory system plays a role in reducing pain.

Topics: Adult; Aged; beta-Endorphin; Electric Stimulation Therapy; Electrodes, Implanted; Endorphins; Female; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Pain, Intractable; Periaqueductal Gray; Radioimmunoassay; Thalamic Nuclei

Chronic implantation of a stimulating electrode in the thalamic relay nucleus (11 cases), in the periaqueductal gray (1 case) and in the internal capsule (2 cases) was performed in fourteen cases which suffered from intractable pain. All these cases could get pain relief at least initial two months. Ventricular fluids were collected before and after stimulation with optimal combination of parameters, and measurements of beta-endorphin were performed by radio-immunoassay. Intrathecal morphine (1mg) injection was performed in eight cases. Cerebrospinal fluids were collected by lumbar tap before and 24 hours after morphine injection. beta-endorphin immunoreactivity was measured by the same method. Pain relief was judged to be excellent if the patient so claimed, and if he discontinued analgesics. Pain relief was thought to be good when it was not completely controllable by stimulation but was sufficiently improved that the patient could do without analgesics. It was thought to be fair when patient could not discontinue analgesics, and poor when patient could not get pain relief. We usually attempt to prevent the stimulation-tolerance by administration of the monoamine precursors , i.e., 1-dopa and 1-tryptophan, on the basis of the experimental observation reported previously. In somatogenic pain patients, the thalamic relay nucleus stimulation was performed in 7 cases (excellent; 3, good; 1, fair; 3) and the periaqueductal gray stimulation in one case (good).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; beta-Endorphin; Electrodes, Implanted; Electronarcosis; Endorphins; Female; Humans; Male; Middle Aged; Neoplasms; Pain, Intractable; Thalamic Nuclei

Immunoreactive beta-endorphin (beta-EP) in the ventricular fluid of six carcinomatous patients was measured using a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation and coagulation of the posteromedial hypothalamus. Samples of ventricular fluid were collected before and after the stimulation and serially after the coagulation. Prior to stimulation, beta-EP-like immunoreactivity (beta-EP-LI) was below 200 pg/ml. In all of the six patients with pain relief, electrical stimulation led to a marked increase in immunoreactive beta-EP. In three patients beta-EP levels remained high after electrical coagulation for 6-24 hrs. These results suggest that beta-EP-like material, released into the ventricular fluid, may contribute to the initial pain blockade that results from stimulation and coagulation of the posteromedial hypothalamus.

Topics: Adult; beta-Endorphin; Chromatography, Gel; Electric Stimulation Therapy; Endorphins; Female; Humans; Hypothalamus; Hypothalamus, Posterior; Male; Middle Aged; Neoplasms; Pain, Intractable; Radioimmunoassay; Time Factors

The effect of large amounts of synthesized human beta-endorphin (beta-EP) administered intrathecally on pituitary-adrenocortical function was investigated by determining the plasma levels of ACTH, cortisol, growth hormone and prolactin in 8 patients with pain caused by severe disseminated cancer. They were divided into 2 groups, an Ep group of 8 patients and a control group of 5 of the same 8 patients. There were no significant effects of beta-Ep on plasma ACTH, cortisol and growth hormone levels. However, the injection of beta-Ep into human subjects resulted in a rise in plasma concentrations of prolactin.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Endorphins; Growth Hormone; Humans; Hydrocortisone; Injections, Spinal; Middle Aged; Neoplasm Metastasis; Pain, Intractable; Pituitary Hormones, Anterior; Pituitary-Adrenal System; Prolactin

Topics: beta-Endorphin; Electric Stimulation Therapy; Endorphins; Humans; Hypothalamus; Hypothalamus, Middle; Pain, Intractable; Stereotaxic Techniques

beta-Endorphin and methionine(met)-enkephalin in cerebrospinal fluid (CSF) were measured before and after removal of an adrenocorticotropic hormone-(ACTH)-secreting adenoma in Cushing's disease by a sensitive radioimmunoassay and a radio-receptor assay, respectively. After tumor resection, the level of ACTH in plasma markedly decreased from 82.6 +/- 22.7 pg/ml to 16.7 +/- 4.1 pg/ml (mean +/- S.E., n = 4). It was found that the level of beta-endorphin in CSF significantly increases from 32.0 +/- 4.5 pg/ml to 61.8 +/- 10.7 pg/ml (P less than 0.05) after tumor resection, while the level of metenkephalin in CSF remained unaltered. This result suggests that hypophysectomy induces an increase of beta-endorphin in CSF.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Endorphins; Enkephalin, Methionine; Enkephalins; Female; Humans; Hypophysectomy; Male; Middle Aged; Pain, Intractable; Pituitary Neoplasms

Topics: Adult; beta-Endorphin; Endorphins; Female; Humans; Hydrocortisone; Injections, Spinal; Male; Middle Aged; Pain, Intractable; Pituitary Hormones

Topics: Adrenocorticotropic Hormone; Aged; Animals; beta-Endorphin; Cerebral Aqueduct; Electric Stimulation; Endorphins; Female; Humans; Male; Middle Aged; Nociceptors; Pain, Intractable; Rats; Self Stimulation; Sensory Thresholds

Immunoreactive beta-endorphin in the third ventricular fluid was measured in response to electrical stimulation of the periaqueductal gray matter in 8 patients with intractable pain during rostral mesencephalic reticulotomy for pain relief. In all patients, marked increase of immunoreactive beta-endorphin was observed. On the other hand, in cases of electrical stimulation of the zona incerta performed during stereoencephalotomy, in 5 patients with involuntary movement, immunoreactive beta-endorphin in the third ventricular fluid did not show any significant change. The authors conclude that the increase of immunoreactive beta-endorphin on electrical stimulation of the periaqueductal gray matter is not a nonspecific response to brain stimulation but a specific response in regard to cerebral localization of endorphins. Direct correlation between pain relief and periaqueductal gray stimulation is also questioned.

Topics: Adult; beta-Endorphin; Cerebral Ventricles; Electric Stimulation; Electric Stimulation Therapy; Endorphins; Female; Humans; Male; Mesencephalon; Middle Aged; Pain, Intractable; Stereotaxic Techniques