Plasma Beta-endorphin Levels Research Articles

Antinociception in the rat induced by a cold environment

Rats placed in a cold environment (4 °C) for 2 h had a sustained increase in tail flick latency (TFL) as well as increase in tail pinch latency (TPch) that was often biphasic with an early peak response at 15 min and a later, often higher, peak at 2 h. Plasma beta-endorphin levels after a modest increase at 5 min (24%) declined throughout the remaining time in the cold. The long-acting opioid antagonist naltrexone had no effect on TFL increases but led to a greater in reases in TPch (P<0.04). In morphine-tolerant rats TFL response was the same as in controls but TPch increases were greater (P<0.04). Rats exposed to 2 h of cold for 17 or 18 consecutive days generally developed tolerance to the analgesia of cold, i.e. TFL and TPch increases were diminished; however, the response to morphine on day 18 was the same as in rats never exposed to cold. Adrenalectomy and hypophysectomy led to significantly smaller increases in TFL (P<0.02andP<0.001, respectively). The TPch response in contrast, was greater in adrenalectomized (P<0.001) and the same in hypophysectomized rats compared to sham controls. An opioid kappa receptor antagonist (Mr 1452) given prior to cold reduced both TFL and TPch response during the first hour. Thus the analgesia induced by cold appeared to shift from an early possibly kappa opioid to a later non-opioid form. The TFL effects seemed to be under hormonal influence while the TPch were not.

Hormonal and Autonomic Reactions to Exercise in Elderly Healthy Subjects and Patients with Ischemic Heart Disease

We have studied the hormonal and vegetative responses to reactions of exercise in 60 healthy subjects (10 young and 50 old) and in 70 patients with ischemic heart disease (IHD) aged 60-74 years. Plasma levels of cortisol, ACTH, met-enkephalins, leu-enkephalins and beta-endorphins were measured by using radioimmunological methods. The state of autonomic control was determined according to spectral analysis of cardiac rhythm. Compared to the young healthy subjects, the older healthy group had an earlier activation of the ACTH-cortisol system and a more pronounced increase in the sympathetic nervous system during sub-maximal exercise. This could be the reflection of a decreased resistance to stress in older age. The elderly IHD patients showed two types of hormonal reactions to exercise: a rise in the cortisol level and a fall in the met-enkephalins (Group 1), or a fall in the cortisol concentration combined with a rise of met-enkephalins (Group 2). In Group I patients a lower exercise capacity and a less economical reaction of the hemodynamics to a workload of 25 watts was found. An excessive activation of the ACTH-cortisol system and a reduced level of blood met-enkephalins in the elderly IHD patients during exercise are thought to be the unfavourable factors promoting a decrease in tolerance to physical load and an impairment of adaptive capacities of the cardiovascular system.

&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.

Influence of endogenous opioids on atrial natriuretic factor release during exercise in man

To evaluate to what extent opioid secretion in exercise induces the release of atrial natriuretic factor (ANF), six healthy male volunteers who were trained subjects, were submitted to two maximal exercise tests with and without (control) opioid receptor blockade by Naltrexone. Blood samples were drawn before (rest) and after exercise (post-exercise) in order to measure human ANF (alpha h ANF), beta-endorphin, plasma aldosterone concentration (PAC) plasma renin activity (PRA) and adreno-cortico trophic hormone (ATCH) by radio-immunological methods. Expired gas was collected during exercise to measure oxygen consumption. On average, the same maximal oxygen consumption (VO2max) during exercise was reached by all subjects with and without treatment. Plasma ANF level at rest slightly decreased after administration of Naltrexone; the response to physical exercise was significantly reduced by Naltrexone. There was no statistical difference between plasma levels of beta-endorphin, PRA and ACTH at rest nor in the post-exercise situation under the influence of Naltrexone. The PAC increased significantly at rest after Naltrexone administration but there was no statistical difference between both values after exercise. These data demonstrate that: (1) ANF secretion during exercise is influenced by the level of beta-endorphin in the plasma; (2) the possible inhibitory role of ANF on aldosterone secretion during exercise is probably over-ruled by the increase in plasma ACTH and PRA.

Relation between Plasma β-Endorphin and the Ventilatory Response to Hypercapnia in Humans

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear. 2. We studied the relationship between circulating immunoreactive beta-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma beta-endorphin and cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma beta-endorphin levels was observed (r = -0.35, P less than 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma beta-endorphin levels (r = -0.36, P less than 0.01). 4. Repetitive hypercapnia prevented the fall in plasma cortisol that occurred under control conditions (P less than 0.02) but had no effect on plasma beta-endorphin. 5. We conclude that plasma beta-endorphin may play a role in the central chemical control of breathing in man.

Experimental approaches to human stress research: Assessment of neurobiological mechanisms of stress in volunteers and psychiatric patients

This article presents a series of experiments that involves the development of three novel strategies for human stress research and the utilization of these strategies to examine neurobehavioral processes of stress in healthy volunteers, schizophrenia, and affective illness. The first strategy involved intravenous 2-deoxy- d-glucose (2DG) administration, a glucoprivic Stressor. We found that glucoprivic stress results in dissociation of hypothalamus—pituitary-adrenal (HPA), adrenomedullary, and sympathoneural activity. In addition, glucoprivic stress in neuroleptic-treated schizophrenic patients caused heightened dopamine activity, as reflected by increased plasma homovanillic acid (HVA) levels and decreased adaptive responses as assessed by decreased food consumption following 2DG administration. These data suggest that neuroleptics do not prevent stress-related increases in dopamine activity and that schizophrenia may be associated with abnormalities in the stress response. The second strategy assessed effects of uncontrollable and identical amounts of controllable stress in volunteers and depressed patients. In volunteers, it was found that uncontrollable in comparison to controllable stress results in specific behavioral and neuroendocrine alterations. Moreover, uncontrollable stress exposure in depressed patients in comparison to volunteers produced greater alterations in behavioral ratings and plasma cortisol levels and that the uncontrollable stress related increases in helplessness ratings and cortisol levels were significantly correlated. These data suggest that depressed patients may have increased sensitivity to uncontrollable stress and that there may be an important interrelationship between the cognitive deficits of depression and the heightened HPA axis activity observed in these patients. Lastly, we used a naturalistic strategy to examine mechanisms relating childhood parental loss and the development of adult affective illness and found that among subjects with early parental loss histories, those who developed adult psychiatric illness had increased resting plasma levels of cortisol and beta-endorphin (ir) as compared with subjects with early loss and no adult history of psychiatric illness. Moreover, increased HPA activity in adulthood was significantly related to poor childhood adjustment to parental loss. The implications of the results of these studies are discussed.

Increased plasma beta-endorphin levels in hereditary angioedema

We measured β-endorphin (BE) and β-lipotropin (BLPH) plasma concentrations (by means of an HPLC-RIA coupled method) during attacks as well as during symptom-free periods in a group of 28 patients with immunochemical (21) or functional (7) C1 inhibitor deficiency. Thirteen patients suffering from chronic urticaria served as controls. Three orders of considerations prompted is to initiate the present study: the clinical relationship between stress and the onset of acute episodes, the possible effects of repeated stressful situations, as are the attacks themselves, on the patients' neuroendocrine system and the well-known existence of close links between the immune system and endogenous opioids. The results show that plasma BE (and, to a lesser extent, BLPH) is dramatically increased during the attacks. In symptom-free periods many patients show very high BE concentrations, often in the presence of slightly elevated concentrations of BLPH and of ACTH. These observations suggest that patients with hereditary angioneurotic edema show a modified pro-opiomelanocortin-synthesizing cell activity that can result in a massive release of BE from the readily disposable pool present in the pituitary and/or an increase in the turnover of the peptide as evaluated by the BLPH/BE ration.

Beta-Endorphin Levels During Pregnancy and Labor

Discovery of the endogenous opiate system of the brain has revolutionized the study of pain and pain management. In this study a convenience sample of 10 pregnant women, 16 nonpregnant women, and 18 men were studied to determine if changes in plasma beta-endorphin-like immunoreactivity affected pain perception during labor. Pregnant women had plasma levels of beta-endorphin significantly higher than nonpregnant women at the midpoint of their menstrual cycle, t = 3.74, df = 31, p = .007. Self-reported pain perception scores were not correlated with plasma beta-endorphin levels. However, as labor progressed, the women reported increased discomfort between contractions and during contractions while beta-endorphin levels increased only slightly. Close examination of the pain pattern indicates that pain perceived by the women between contractions increased at a greater rate than during contractions. This pattern suggests that opiate-active beta-endorphin may increase the ability of women to tolerate acute pain.

Effects of treadmill running on plasma beta-endorphin, corticotropin, and cortisol levels in male and female 10K runners

Reports of plasma beta-endorphin (B-EN) levels in response to submaximal exercise have been highly disparate. Variations in experimental design have complicated interpretation of previous research. The present study was designed to determine whether a sequential change in plasma beta-endorphin (B-EN), corticotropin (ACTH), and cortisol levels occurs in response to a 30-min submaximal run. Twenty-three subjects were divided into four groups: male runners, female runners, sedentary males and sedentary females. Subjects ran on a treadmill at 80% of previously determined maximum heart rate. Five plasma samples were obtained through an indwelling catheter before exercise (-30 and 0 min), at 15 and 30 min of exercise, and after 30 minutes of recovery. The run resulted in no rise in B-EN, ACTH, and cortisol despite an elevated rectal temperature. B-EN values were significantly higher in males than in females (p less than 0.01). No sex or training differences were seen with respect to change of hormone concentrations over the course of the run. Three male runners developed symptoms of vasovagal syncope after the catheter placement and had high initial B-EN, ACTH, and cortisol concentrations which decreased throughout the run. These data indicate that gender and training do not affect ACTH and cortisol concentrations before, during, and after 30 min of treadmill running at 80% of maximum heart rate, whereas B-EN concentrations are higher in males under these conditions.

Plasma beta‐endorphin concentrations during suckling in lactating women

Beta-endorphin appears to be involved in the hormonal response to suckling in some animals. The peripheral secretory patterns of beta-endorphin, prolactin and cortisol were investigated in serial venous blood samples taken during suckling from eight healthy women who were breast-feeding on the third or fourth day of the puerperium. Plasma levels of prolactin and beta-endorphin increased significantly during suckling reaching a peak after 20 min, levels of cortisol remained unaffected. It is suggested that the increased beta-endorphin derives from an extra-hypophyseal source.

Neuroendocrine Responses to Physostigmine in Alzheimer's Disease

To assess central nervous system cholinergic neuroendocrine regulation in Alzheimer's disease (AD), we measured plasma arginine vasopressin, beta-endorphin, and epinephrine responses to a cholinergic challenge elicited by intravenous administration of the acetylcholinesterase inhibitor physostigmine (0.0125 mg/kg) in male patients with AD (n = 12) and compared their responses with those of age-matched normal control subjects (n = 12). Physostigmine promptly increased plasma arginine vasopressin (tenfold), beta-endorphin (twofold to threefold) and epinephrine (threefold) levels in elderly control subjects. In contrast, patients with AD showed attenuated responses to physostigmine. When controls and patients with AD who experienced nausea (n = 2 and n = 6, respectively) were excluded, the arginine vasopressin, beta-endorphin, and epinephrine responses of patients with AD were significantly less than those of control subjects. These data suggest that the central nervous system cholinergic deterioration of AD results in decreased responsiveness of neuroendocrine systems that are regulated by central cholinergic mechanisms.

Beta-endorphin in experimental canine spinal ischemia.

Plasma and cerebrospinal fluid beta-endorphin concentrations were radioimmunologically assayed in dogs subjected to spinal cord ischemia induced by infrarenal aortic ligature and in control sham-operated dogs. Plasma beta-endorphin levels rose significantly following surgery in control dogs but were unaffected by spinal ischemia. On the other hand, a significant increase in cerebrospinal fluid beta-endorphin concentration occurred after spinal ischemia, while surgical stress had no significant effect. Thus, the origins of plasma and cerebrospinal fluid beta-endorphin may be different, with the former secreted from the hypophysis and the latter from nervous tissue. Observed changes in cerebrospinal fluid beta-endorphin concentration could be related to the ischemic lesion of nervous tissue while the changes in plasma levels may reflect general stressing factors such as the surgery in our experiments.

Plasma beta-endorphin in patients on maintenance hemodialysis

A sensitive and specific radioimmunoassay for beta-endorphin without gel filtration of plasma extracts has been developed by using newly raised antibody. The minimal detectable quantity was 5 pg, and ED 50 was 23 pg/ml. The crossreactivity of antibody with beta-lipotropin was 3.3%, but not showed crossreaction with other fragments of beta-lipotropin, beta-MSH and ACTH. The inter-assay coefficient of variation was 2.7% to 17.4%, and the intra-assay coefficient of variation was 4.5% to 26.4%, respectively. The mean recovery for unlabeled beta-endorphin added to plasma and extracted was 92.1% to 110.4%. Plasma levels of beta-endorphin in 40 normal subjects was 14.7 +/- 3.1 pg/ml and 14.8 +/- 1.1 pg/ml in 10 patients with chronic glomerulonephritis whose renal function was normal. There was no significant difference between the two groups. On the other hand, plasma levels of beta-endorphin in 16 patients on maintenance hemodialysis was significantly increased of 56.3 +/- 6.3 pg/ml than the other two groups. Physiological role of this high beta-endorphinemia in patients on maintenance hemodialysis still remains to be resolved.

Acute and chronic ethanol treatment on beta-endorphin and catecholamine levels

The effect of acute (2.0 g/kg, intragastrically) and chronic (8.0–11.0 g/kg/day for 10 days, intragastrically) ethanol exposure on beta-endorphin levels in plasma, hypothalamus and pituitary were examined in rats. Hypothalamic and plasma catecholamines and plasma corticosterone were also measured in these animals. Plasma beta-endorphin, norepinephrine (NE) and corticosterone levels were significantly increased and dopamine (DA) was unchanged in acute and chronic ethanol-treated rats. Compared to controls, plasma epinephrine (E) levels were increased in acute ethanol-treated rats but no significant change was observed in chronic ethanol-treated rats. Plasma dopamine were significantly decreased following chronic ethanol treatment while no significant change was observed after acute treatment. In the hypothalamus, beta-endorphin and dopamine contents were increased and norepinephrine levels were reduced in response to ethanol exposure. Beta-endorphin levels were decreased significantly in the anterior pituitary and the neurointermediate lobe of the pituitary in ethanol-treated animals except in the neurointermediate lobe of the chronic ethanol-treated animals. These findings together suggest that there is an interaction between beta-endorphin, catecholamines, corticosterone and ethanol in response to acute and chronic ethanol exposure in rats.

Acupuncture and Sensory Thresholds

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

Interaction of stress and ethanol: effect on beta-endorphin and catecholamines.

To examine the interaction of ethanol (ET) and stress on beta-endorphin and catecholamine (CA) levels, male rats pretreated with ET (3.0 g/kg, i.p.) or saline were immobilized for 30 min and killed 90 min after the initial injection. Stress resulted in (a) an increase in plasma levels of norepinephrine (NE, 243%), epinephrine (E, 175%), beta-endorphin (220%) and corticosterone (CS, 151%) and a decrease in dopamine (DA, 54%); (b) a decrease in hypothalamic NE (15%) and beta-endorphin (33%) levels and an increase E (23%) and DA (58%) levels; (c) a decrease in pituitary beta-endorphin levels in both the neurointermediate (23%) and anterior (131%) lobes. Treatment with ET resulted in: (a) an increase in plasma NE (81%), E (53%), CS (71%), and beta-endorphin (33%) levels and decrease in DA (54%); (b) a decrease in the hypothalamic NE (12%) levels and an increase DA (27%) and beta-endorphin (46%) levels, and (c) a decrease in beta-endorphin (15.5%) in the intermediate lobe of the pituitary. Treatment with ET of stressed animals had only a small effect: (a) in plasma NE, E, CS, and beta-endorphin levels decreased by 30, 31, 14, and 36%, respectively; (b) in the hypothalamus DA levels decreased by 40% and beta-endorphin increased by 71%; (c) in the pituitary beta-endorphin increased in both the intermediate lobe (25%) and anterior (50%) lobes. Thus when the data of the stressed ET-treated group is compared to that of the nonstressed saline injected group, none of the measures differ significantly. These results confirm our earlier work indicating a significant interaction of ET and stress.

Dopaminergic—opioidergic interaction is reflected by changes in pituitary hormone secretion in patients with essential hypertension

In a randomized, double-blind crossover study 13 untreated patients with mild essential hypertension were exposed to submaximal bicycle exercise. Sixty minutes before ergometry 10 mg metoclopramide or placebo, and 10 min before exercise 0.4 mg naloxone or placebo, were given intravenously. Plasma adrenocorticotrophic hormone, beta-endorphin and cortisol levels increased significantly after ergometry, whether performed after placebo, naloxone, metoclopramide or metoclopramide + naloxone treatment. However, only naloxone administration potentiated plasma adrenocorticotrophic hormone, beta-endorphin and cortisol responses to workload. Plasma levels of adrenocorticotrophic hormone, beta-endorphin and cortisol were 45 +/- 14 pg/ml, 6.2 +/- 1.2 pmol/l and 141 +/- ng/ml, respectively, after ergometry, when performed after placebo, but these values were increased to 61 +/- 10 pg/ml, 11.4 +/- 2.8 pmol/l and 207 +/- 22 ng/ml, respectively, after naloxone treatment. This naloxone-induced potentiation of hormonal release was blocked by metoclopramide pretreatment, suggesting a close interaction between dopaminergic and opioidergic mechanisms, regulating hormonal responses to physical exercise.

Immunoreactive ACTH, beta-endorphin, and cortisol levels in plasma following spinal manipulative therapy.

This study examines the possibility of a humorally mediated analgesic response to spinal manipulative therapy by determination of plasma levels of beta-endorphin, adrenocorticotropic hormone (ACTH), and cortisol before and after intervention. Forty male subjects (20 symptomatic, 20 asymptomatic) were allocated into four equal groups. Two treatment groups were given spinal manipulative therapy, and two groups underwent a sham procedure. Blood samples were taken via indwelling butterfly needles pre- and postintervention in all four groups, and levels of immunoreactive ACTH, immunoreactive beta-endorphin, and cortisol determined by radioimmunoassay. No differences in ACTH or beta-endorphin were found between sham and treated groups, or between pre- and postintervention in any group; cortisol levels fell over the course of the study in all groups. The findings thus appear to exclude a humoral role for beta-endorphin in mediating the analgesic response to spinal manipulative therapy; in addition, they suggest that such therapy is not a stressor that activates the hypothalamo-pituitary-adrenal axis.

Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children.

In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.

Neuroendocrine and cardiovascular responses to high-dose corticosteroid therapy in canine endotoxin shock.

The neuroendocrine and cardiovascular responses to endotoxin administration and the effects of subsequent high-dose corticosteroid therapy have been investigated in dogs. Shock was induced in anaesthetised animals by a large bolus of E. coli endotoxin (5 mg/kg) followed by a continuous infusion (2 mg/kg per hour). One hour after induction of shock, the circulating volume was expanded using a colloidal gelatin solution. Fifteen minutes later, one group of five animals received a bolus of methylprednisolone sodium succinate 30 mg/kg, while a control group of five animals was given an equivalent volume of isotonic saline. The administration of endotoxin produced reductions in mean arterial pressure, cardiac index and left ventricular dp/dtmax, together with increases in systemic and pulmonary vascular resistances. These haemodynamic changes were associated with increases in arterial plasma levels of adrenaline, noradrenaline, cortisol, immunoreactive beta-endorphin and immunoreactive metenkephalin. Cardiovascular improvement followed volume replacement and was associated with reductions in circulating catecholamines. No significant haemodynamic or neuroendocrine changes were demonstrated in the 2 h following steroid therapy.