Endorphin Levels Research Articles

Beta endorphin levels during heroin, methadone, buprenorphine, and naloxone challenges: Preliminary findings

Beta endorphin (BE) is a polypeptide agonist for the brain's endogenous opioid system. Levels of BE are elevated by opioid antagonists such as naloxone and depressed by short-acting agonists such as heroin and morphine; they become normalized during steady-state methadone. Buprenorphine (BUP) is a partial opioid agonist whose effects on BE levels were examined in six former heroin addicts and 14 methadone-maintained patients before and after being switched to sublingual BUP 2 mg daily for 1 month. In six former methadone-treated subjects BE levels also were measured after stopping BUP and after naloxone challenge. Levels of BE were not significantly lower in subjects started on BUP after stopping heroin (n = 6) (8.0 versus 8.1 ng/ml) or in subjects started on BUP after stopping methadone (n = 14) (11.6 vs 15.6 ng/ml). However, BE levels were lower on BUP than after naloxone challenge (n = 6) (7.0 versus 34.9 ng/ml). Levels of BE did not significantly change between the first 2 weeks (“early”) and “later,” although BE levels on methadone significantly correlated with BE levels on BUP in the “early” but not the “later” phase. The BE levels on BUP also did not differ from BE levels of unmedicated normals.

The Effects of General , Spinal and Epidural Anesthesia on Maternal and Umbilical Cord Plasma beta- endorphin Level

The Effects of General , Spinal and Epidural Anesthesia on Maternal and Umbilical Cord Plasma beta- endorphin Level

Changes in beta-endorphin levels in response to aerobic and anaerobic exercise.

Exercise-induced increases in the peripheral beta-endorphin concentration are mainly associated both with changes in pain perception and mood state and are possibly of importance in substrate metabolism. A more precise understanding of opioid function during exercise can be achieved by investigating the changes in beta-endorphin concentrations dependent upon intensity and duration of physical exercise and in comparison to other stress hormones. Published studies reveal that incremental graded and short term anaerobic exercise lead to an increase in beta-endorphin levels, the extent correlating with the lactate concentration. During incremental graded exercise beta-endorphin levels increase when the anaerobic threshold has been exceeded or at the point of an overproportionate increase in lactate. In endurance exercise performed at a steady-state between lactate production and elimination, blood beta-endorphin levels do not increase until exercise duration exceeds approximately 1 hour, with the increase being exponential thereafter. beta-Endorphin and ACTH are secreted simultaneously during exercise, followed by a delayed release of cortisol. It is not yet clear whether a relationship exists between the catecholamines and beta-endorphin. These results support a possible role of beta-endorphin in changes of mood state and pain perception during endurance sports. In predominantly anaerobic exercise the behaviour of beta-endorphin depends on the degree of metabolic demand, suggesting an influence of endogenous opioids on anaerobic capacity or acidosis tolerance. Further investigations are necessary to determine the role of beta-endorphin in exercise-mediated physiological and psychological events.

Exercise-Induced Changes of Endorphin Contents in Hypothalamus, Hypophysis, Adrenals and Blood Plasma

Changes of alpha-, beta-, and gamma-endorphin contents were determined in hypothalamus, hypophysis, adrenals and blood plasma in Wistar rats. Four hours of swimming in water at 32 +/- 1 degrees C caused a decrease of the beta-endorphin content in hypophysis and hypothalamus. In adrenals, beta-endorphin did not change. Changes of alpha- and gamma-endorphins were not parallel to alterations of beta-endorphin. In blood plasma, levels of both alpha- and gamma-endorphins were elevated. After 7 days of swim training, 4 hours of swimming caused a slight increase of alpha-, beta- and gamma-endorphin levels in hypophysis as well as a pronounced increase of alpha- and beta-endorphins in adrenals. In hypothalamus, beta-endorphin content was decreased, but alpha-endorphin content was on the level of sedentary controls, gamma-endorphin content doubled. The levels of endorphins in blood were higher than after a single swimming bout. It was concluded that during acute exercise the activation of the opioid system is mainly based on the augmented release of beta-endorphin. In daily repeated exercise the production of beta-endorphin increases and exceeds the elevated release in hypophysis and adrenals.

The Influence of Photoperiod on the Hypothalamic Content of Beta‐Endorphin and the Luteinizing Hormone Responses to Naloxone and to Steroid Withdrawal in the Male Syrian Hamster

Abstract The aim of this study was to investigate the influence of inhibitory photoperiods upon opioidergic function, as determined by changes in the hypothalamic content of beta-endorphin and the luteinizing hormone response to opioidergic receptor blockade, in the male Syrian hamster over the course of gonadal involution and spontaneous gonadal recrudescence. Animals exposed to an 8 h light: 16 h dark cycle (8L: 16D) for 14 weeks underwent gonadal regression. Regression was also observed in animals held for 7 weeks on one of a range of short daylengths of between 11.5 h and 13.5 h, the degree of atrophy being greatest in those animals on the shortest daylength. The tissue concentration of beta-endorphin within the mediobasal hypothalamus was significantly higher in animals exposed to 8L: 16D for 14 weeks than in gonadally active controls held on long days (16L: 8D). Exposure to photoperiods of less than 13.5 h for 7 weeks also caused a significant increase in the beta-endorphin content of the mediobasal hypothalamus and there was a positive correlation between the concentration of beta-endorphin, the degree of gonadal atrophy and the shortness of the photoperiod. Endorphin levels within the preoptic area were not affected by photoperiodic treatments. Exposure of intact animals to 8L: 16D for 12 weeks caused gonadal atrophy and an associated loss of the luteinizing hormone responses to both naloxone and castration. Castrated animals receiving testosterone replacement (cast + T) also exhibited photoinhibition, in the form of reduced serum levels of luteinizing hormone, and this was similarly accompanied by a loss of sensitivity to naloxone and to withdrawal of steroid. Prolonged exposure to 8L:16D led to spontaneous reactivation of the gonadotrophic axis as a consequence of the development of scotorefractoriness. In both gondally intact animals and in cast + T groups, this was associated with a restoration, in parallel, of the luteinizing hormone responses to naloxone and to castration/ steroid withdrawal. The time-course of the restoration of the response to steroid withdrawal in castrates was not significantly different to that observed in intact animals. The luteinizing hormone response to naloxone took significantly longer to redevelop in cast + T groups than it did in gonadally intact animals. The data demonstrate that central opioid systems are sensitive to photoperiod and are consistent with the hypothesis that opioids are involved in the neuroendocrine regulation of reproductive responses to daylength.

Serumβ-endorphin levels in chronic pelvic pain patients

β-Endorphin is a 31 amino acid opioid peptide with several physiologic roles of which analgesia is one. Numerous reports relate stress in humans to an increase in β-endorphin levels, suggesting a role for the peptide as a pain modulator. In chronic pain patients, elevated as well as reduced β-endorphin levels have been reported. The pharmacopathology, if any, of chronic pelvic pain remains unclear. This study is to investigate the levels of serum β-endorphin in chronic pelvic pain patients in relation to their perception of pain intensity. Twenty-three patients undergoing diagnostic laparoscopy for chronic pelvic pain were studied. Ten control patients were chosen from patients scheduled for elective laparoscopy sterilization who had no previous history of pelvic pain. Patients were asked to indicate their perception of pain intensity, using a visual analog scale, numbered one to ten. Laparoscopy was performed on all patients, with documentation of location, density of adhesions, and/or the presence of other pelvic pathology. All blood samples were drawn on the morning of surgery prior to laparoscopy. Results indicated a significantly (Ρ < 0.01) higher serum β-endorphin level in chronic pelvic pain patients compared to controls. The mean was 14.8 pg/ml ± 13.2 SD for pain patients and 4.3 pg/ml ± 3.0 SD for controls. There were significantly more pelvic adhesions (Ρ < 0.01) and pathologic abnormalities (Ρ < 0.001) upon laparoscopic examination in the study group than controls. Of particular interest is an inverse correlation between subjective pain levels and serum β-endorphin levels, i.e. the higher β-endorphin level, the lower the perception of pain. Our data suggest a role for β-endorphin in the modulation of chronic pelvic pain, i.e. of an opiate response to chronic-pelvic pain. An elevation of β-endorphin level appears to decrease the patient’s perception of chronic pain. This response, providing the body with its own natural analgesic, would be in agreement with the well-documented role of this peptide in relieving acute pain in patients.

Plasma β-endorphin level in cases of luteal phase defect

To evaluate beta-endorphin secretion in euprolactinemic cases of luteal phase defect (LPD). Serial blood samples from the 18th to the 26th day of the menstrual cycle were assayed for beta-endorphin, progesterone (P), estradiol (E2), and prolactin (PRL) in cases of LPD and controls. Diagnosis of LPD was based on determinations of serum P and premenstrual endometrial biopsy. From Cairo University Hospitals. PATIENT, PARTICIPANTS: Twenty-six women with LPD and 8 normal fertile women (controls) were chosen. None. beta-Endorphin, P, E2, and PRL concentrations were determined by the corresponding 125I radioimmunoassay. Plasma beta-endorphin level in cases of LPD varied from 2.58 to 9.14 pmol/L, whereas the level of controls varied from 2.41 to 5.57 pmol/L. The mean value of plasma beta-endorphin in cases of LPD was significantly higher than that of controls by 146% (P less than 0.0005). In spite of the significant decrease of serum P in cases of LPD, serum E2 level did not differ significantly from that of controls. The possible sources of beta-endorphin rise and its implication in the etiology of LPD are explained.

Experimental pain thresholds and plasma beta-endorphin levels during exercise

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.

Persistently low natural killer cell activity and circulating levels of plasma beta endorphin: Risk factors for infectious disease

Beta endorphin levels were quantitated in plasma samples obtained from normal subjects (n=81, 37% males and 63% females, age range 18–45 years) as a component of a prospective study examining the relationship of illness morbidity to natural killer cell activity and psychological indices of stress. The present study was designed to test whether beta endorphin levels contributed additionally to the explanation of illness outcome variance. In the larger study, persistently low NK (LNK) activity was associated prospectively with higher illness morbidity. The findings reported here suggest that the observed LNK activity might be affected by circulating levels of plasma beta endorphin, as lower endorphin levels predicted the LNK pattern, which in turn, predicted higher illness morbidity.

Elevated plasma beta-endorphin levels in patients with congestive heart failure

Recent experimental studies show that the opioid system is important to the pathophysiology of cardiovascular impairment in congestive heart failure. Plasma beta-endorphin levels were measured in 37 patients with congestive heart failure and compared with those of 21 age- and gender-matched normal subjects. The relation of plasma beta-endorphin levels and cardiac function at rest and exercise capacity was assessed in 17 of the patients with dilated cardiomyopathy. Exercise capacity was determined by symptom-limited maximal treadmill exercise with expired gas analysis. Plasma beta-endorphin levels were elevated and correlated with the patients' New York Heart Association functional cardiac status (control: 14.0 ± 4.4 pg/ml; class II: 17.9 ± 3.6 pg/ml; class III: 28.3 ± 8.8 pg/ml; class IV: 46.7 ± 14.6 pg/ml, mean ± SD). No relation was found between plasma beta-endorphin levels and left ventricular systolic performance as assessed by M-mode and Dopler echocardiography. Plasma beta endorphin levels were negatively correlated with cardiac output determined by Doppler echocardiography and positively correlated with systemic vascular resistance (r = −0.733, r = 0.747, respectively, both p < 0.001), but not correlated with calf blood flow as measured by a plethysmography. A good correlation was found between plasma beta-endorphin levels at rest and exercise capacity. The correlations with peak oxygen consumption, anaerobic threshold, and peak rate-pressure product were r = −0.721, −8.672, and −0.674, respectively (p < 0.01).The data show that plasma beta-endorphin levels are elevated in patients with congestive heart failure and reflect, to some degree, the severity of the disease.

Decreased beta endorphin levels in peripheral blood cells of multiple sclerosis patients

Decreased beta endorphin levels in peripheral blood cells of multiple sclerosis patients

Decreased beta endorphin levels in peripheral blood cells of multiple sclerosis patients

Decreased beta endorphin levels in peripheral blood cells of multiple sclerosis patients

Negative allesthesia and decreased endogenous opiate system activity in anorexia nervosa

The combined effects of an intragastric load of glucose compared to water and of naltrexone compared to placebo were tested on preference for sucrose in six anorectic patients. While in normal subjects, glucose-induced negative allesthesia is known to disappear upon loss of weight, it persisted in anorexia nervosa (AN) despite a major weight loss; furthermore, in contrast with its effects in normoponderal subjects, naltrexone at the dose of 25 mg did not decrease the preference for sucrose nor did it enhance glucose-induced allesthesia. Basal plasma beta endorphin level determined by radioimmunoassay was higher in AN than in normal subjects (75±6.1 pmoles/l vs. 13±3.8 pmoles/l) ( p<0.001). It is suggested that a decrease in endogenous system opiate activity might be associated with food refusal and body weight loss in anorexia nervosa.

Effect of piracetam on sensitivity to pain, blood?-endorphin level, and cerebral corticalcAMP level in rats

Cathepsin D localization was studied in the liver of white rats by ultrastructural cytochemistry. It was shown that the product of reaction was present in lysosomes of hepatocytes, Kupffer's and endothelial cells and in fibroblasts from portal tracts am small granules or their conglomerate of different electron density. The lowest activity of cathepsin D was observed in hepatocytes, the most intensive reaction--in Kupffer cells. The extracellular activity of cathepsin D in vivo was revealed. It means that besides participation in intracellular degradation of different proteins, cathepsin D is secreted to extracellular space by liver cells (hepatocytes, Kupffer cells, fibroblasts) and it may participate in catabolism of intercellular matrix.

&amp;beta;-Endorphin Levels in the Follicular Fluid of Human Oocytes Fertilized in vitro

This study was carried out in order to investigate the relationship between beta-endorphin (beta-ep) levels in plasma and follicular fluid and fertilization rates of oocytes from women undergoing treatment in our in vitro fertilization and embryo transfer program. Nine women suffering from severe tubal damage, with regular menstrual cycles, were studied. Follicular growth was induced with clomiphene citrate, combined with human menopausal gonadotropins. Analysis of follicular fluids and plasma showed no significant difference in beta-ep levels. The larger follicles (greater than 2 ml volume) had significantly higher beta-ep levels than smaller follicles (less than 2 ml volume; p less than 0.001); however, there was no significant difference in the fertilization rates of their oocytes.

Effects of an angiotensin converting enzyme (ACE) inhibitor on plasma endorphin level

1. In addition to their antihypertensive effect, ACE inhibitors have been reported to increase general well-being, general health and vitality and work performance. The cause of these effects is not known. A possible mechanism may be release of β-endorphins. 2. In the present study changes in plasma concentration of β-endorphins on days with ACE inhibitor treatment ( n = 12) and on non-treatment control days ( n = 12) were compared in 6 patients. 3. Both on control and treatment days the β-endorphin level fell, by 7.1 and 10.0%, respectively, from 8.00 a.m. to 8.00 p.m., reflecting the known diurnal rhythm of this opioid. This difference between the control and treatment days is not statistically significant. 4. The study should be extended to determine endorphin concentration in the cerebrospinal fluid, and other opioids should be looked for.

Quantitative relationships between pain intensities during labor and beta-endorphin and cortisol concentrations in plasma. Decline of the hormone concentrations in the early postpartum period

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.

Effects of naloxone on prolactin, growth hormone and cortisol response to insulin hypoglycemia in obese subjects.

Recent studies suggest that opioid peptides may influence the secretion of pituitary gland hormones. Since obese patients often show impaired growth hormone (GH), prolactin (PRL) and cortisol responses to stimuli and raised beta endorphin levels, the opioid regulation of such hormone secretion could be different from that in normal weight subjects. In order to verify this hypothesis we studied the effect of iv naloxone, an opiate receptor antagonist, on GH, PRL and cortisol response to insulin-induced hypoglycemia in 9 obese female subjects. Seven normal weight females were used as control group. A control test using saline showed that the PRL and GH responses to insulin stress were impaired in obese subjects, whereas no difference was seen in the cortisol response. Naloxone did not modify the PRL and GH response but provoked a rise in the cortisol response in both obese and normal weight subjects. These findings suggest that while the opioid peptides do not play an important role in regulating the GH and PRL response to insulin hypoglycemia, they influence the cortisol response. In obese patients the impairment in GH and PRL response to stimuli cannot be related to alterations in opioid peptide regulation.

Effect of Naloxone on Maximal Exercise Performance and Control of Ventilation in COPD

Elevated endorphin levels in patients with COPD may act to diminish the sensation of dyspnea. Exogenous opioids decrease exertional dyspnea and increase exercise capacity in COPD patients. The purpose of this study was to determine the effects of endogenous opioids on the exercise capacity and control of breathing in patients with COPD. We hypothesized that naloxone, an opioid antagonist, would block the endogenous endorphins and decrease the exercise capacity of our patients. Six patients (mean age, 58.8 +/- 3.2 years) with COPD (mean FEV1, 1.28 +/- 0.46 L) underwent identical incremental cycle ergometer tests to exhaustion (Emax) and assessment of their hypercapnic and hypoxic ventilatory responses and mouth occlusion pressure responses following the IV administration of naloxone (0.4 mg/kg) (N) or placebo (P) in a randomized, double-blind fashion. Perceived dyspnea (modified Borg scale), breathing patterns, and expired gas levels were compared at rest and at maximal workload (WL). There was no significant difference after N compared with after P in the WL or the duration of work. At Emax there were no significant differences after N compared with after P in ventilation, the level of dyspnea, P0.1, VO2, or VCO2. The ventilatory response to CO2 production during exercise (delta VE/delta VCO2) and the ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia did not differ significantly after N compared with after P. This study does not support the hypothesis that endogenous opioids play a significant role in dampening dyspnea and facilitating exercise in patients with COPD.

Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis

Expression of mRNAs coding for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta-endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.