Endorphin Levels Research Articles

Endorphins in inbred mice with variable sensitivity to ethanol: Effect of acute ethanol treatment

Resting levels of B-endorphin like immunoreactivity were determined in the hypothalamus, neurointermediate lobe and anterior lobe of the pituitary gland and the serum of inbred mice strains ( C57BL 6 , BALB C and DBA 2 ). C57BL 6 mice showed the highest content of B-endorphin like immunoreactivity in the neurointermediate lobe, anterior lobe and serum. Animals were injected i.p. with either an ethanol solution (3g ethanol/Kg b. wt.) or saline. 45 minutes post ethanol treatment the B-endorphin like immunoreactivity content was increased in the serum of all three strains of mice studied and was decreased in the hypothalamus of the C57BL 6 mice. Studies with reverse phace HPLC indicated some differences in the relative proportions of the various forms of B-endorphin in some tissues among the three strains of mice. These results suggest that genetically determined differences in endorphin levels may be involved in some of the genetically determined differences in responses to ethanol.

Effects of intracranial self-stimulation on brain opioid peptides

The neurochemical system(s) underlying brain stimulation reward (ICSS) has been investigated for many years. The catecholamine hypothesis is currently most accepted with predominant emphasis on the role of dopamine. The present report examines the role of three opioid peptides—Methionine and Leucine Enkephalin (ME and LE) and β-Endorphin (β-E) in this behavior. Peptide levels from piutitary, hypothalamus and whole brain were determined by independent RIAs and analyzed according to treatment: low, moderate and high ICSS responders, sham controls, animals receiving nonspecific stimulation, and naloxone—with and without ICSS. Not only did naloxone reduce ICSS from high responders by 74%, it also was able to reduce peptide levels—most notably for ME and βE in most regions. Additionally, the effects of ICSS on endorphin levels was found to be related to the rate category of responding. Since endorphins are known to interact with dopamine systems, it is therefore considered likely that the endogenous opioid peptides play an important role in ICSS either directly or indirectly via their influence on catecholamine systems.

Causal links between plasma and CSF endorphin levels in stress: Vector-ARMA analysis

To explore causal links between vital sign responses and immunoreactive beta-endorphin (“i-BE”) rises in blood and CSF during ovine endotoxin stress, we analyzed concurrent i-BE levels in these two compartments by a “vector-ARMA” (=autoregressive moving average) method. This technique—widely used for modeling in other applications—has not to our knowledge been employed to study dynamic relationships of neuropeptides. Log-transformed i-BE levels were first “filtered” by repeated observations ANOVA to confirm significance of rises in both compartments. Next, vector-ARMA methodology was applied to derive an optimal causal model of vital sign changes and i-BE entry into plasma vs. CSF pools. The model indicated that reflux of i-BE from blood into CSF contributed to increases in CSF levels of this hormone. This novel application to neuroendocrinology of this approach illustrates its utility in evaluating changes in one or more neuropeptide levels in multiple compartments to indicate potentially causal relationships.

?-Endorphin and endogenous ethanol blood levels in patients with alcoholism

?-Endorphin and endogenous ethanol blood levels in patients with alcoholism

The effect of labour and epidural analgesia on pain threshold.

Pain thresholds were measured using forehead pressure in 30 women before amniotomy and then during labour up to the point of their requesting analgesia. Measurements continued subsequently only in those having epidural analgesia alone. No significant change in pain threshold was seen in any patient up to the administration of analgesia, nor thereafter in the ten patients having epidurals. This study fails to confirm previous reports in animals of significant rises in pain threshold during parturition. It calls into question the view that previously reported changes in plasma endorphin levels may be associated with altered pain thresholds.

Naloxone: Effects on hypoxic pulmonary vasoconstriction

To determine the effect of naloxone on the hypoxic pulmonary vasoconstrictive response, six mongrel dogs were rendered hypoxic with 10% oxygen and were given either saline or naloxone. Following hypoxia all dogs had significant increases in mean pulmonary artery pressure (PAP) and pulmonary arterial resistance index (PARI) without changes in cardiac output or systemic blood pressure. Beta endorphins did not change at any time following hypoxia. Dogs receiving naloxone had significant lowering of PAP and PARI without changes in plasma beta endorphin levels. We conclude that naloxone attenuates hypoxic pulmonary vasoconstriction without measurable alterations of plasma beta endorphin levels.

Effect of percutaneous transcerebral electrical stimulation during electroanesthesia on CSF and plasma ?-endorphin levels

Effect of percutaneous transcerebral electrical stimulation during electroanesthesia on CSF and plasma ?-endorphin levels

The radioimmunoassay of α-melanocyte-stimulating hormone and endorphin in trout ( Salmo gairdneri) and the effect of blinding on the plasma levels of these peptides

Direct radioimmunoassays for α-melanocyte-stimulating hormone (α-MSH) and endorphin in trout plasma were established and validated. The equilibrium plasma levels of both α-MSH and endorphin were found to be significantly higher in blind than in intact trout maintained under identical conditions. These differences were accompanied by differences in body colour, the blind fish being very much darker than the intact fish.

The Measurement of Endorphins in Body Fluids

The measurement of endorphins in body fluids has been an important advance in clinical research attempting to link the endogenous opioid system to psychiatric illness and symptomatology. The consideration of methodologic differences in assay technique and in clinical methods is important in evaluating results of studies. Whereas findings in early clinical studies supported the notion of increased endorphin system function in patients with schizophrenia, cumulative data from the considerable number of studies carried out throughout world centers have been unable to demonstrate a consistent abnormality in levels of endorphins in CSF or plasma of patients with schizophrenia. Among the affective disorders, data suggest the possibility of relative changes in levels of opioids within individual manic-depressive patients when studied across state change from depression to mania. In studies of depressive illness there is accumulating evidence that the endogenous opioid system may relate or contribute to abnormality of the HPA axis. In our work measuring opioids in CSF we have observed relationships between anxiety and CSF opioids in normals and psychiatric patients and changes in CSF opioid activity in patients with anorexia nervosa accompanying weight change. These data are consistent with other evidence linking endorphins to CNS noradrenergic systems and to biologic response to stress.

Endorphin levels in cerebrospinal fluid of patients with postoperative and chronic pain : Anesthesiology, 57 (1982) 1–4

Pain: June 1983 - Volume 16 - Issue 2 - p 215-216 doi: 10.1016/0304-3959(83)90223-3

Morphine tolerance is associated with elevated levels of an uncharacterized endorphin (peak B) in mouse brain with no change in 3H-dihydromorphine binding

A partially characterized mouse brain endorphin was shown to be elevated (p 0.01 U-Test) in ICR strain mice that had been made tolerant but not dependent upon morphine (5 mg/kg sc., given for 32 days). The animals were tolerant to the antinociceptive effect of morphine as judged by the tail immersion assay (48°C) but showed no detectable dependence or withdrawal syndrome effects following the administration of naloxone (writhing, jumping, diarrhea or hypermotility) on day 33. No significant changes were seen in any other mouse brain endorphins (p 0.05 U-Test). Also there was no apparent change in the number or binding properties of 3H-dihydromorphine ( 3H-DHM) receptors (μ-receptors) in chronic morphine (CM) treated, as compared with chronic saline (CS) treated animals.

Cold stress in the rat induces parallel changes in plasma and pituitary levels of endorphin and ACTH

Endorphin and ACTH-like materials levels in rat plasma and pituitary were measured by radioimmunoassay under baseline and cold stress conditions. Cold stress significantly increased plasma beta-endorphin and ACTH immunoreactivity. A rise in these two peptides was also found in the neurointermediate lobe of the pituitary, while in the anterior lobe their levels were unaffected. These findings suggest that the rise of beta-endorphin and ACTH content in the neurointermediate lobe occurs as a compensatory biosynthetic mechanism for the peptides released from the adenohypophysis.

Endorphin levels in opioid-dependent human subjects: a longitudinal study.

Endorphin levels were measured in 51 cerebrospinal fluid samples from 27 opioid-dependent or postdependent subjects. Radioreceptor assay showed the endorphin levels to be higher than those found in normal subjects. These high levels were found even while subjects were on methadone maintenance. The duration of opioid dependence was positively correlated with fraction I values. Both fractions tended to be lower during early withdrawal than late withdrawal. In naltrexone-maintained patients, radioreceptor assay showed FII to be greatly elevated, but electrophoresis and HPLC indicated that the elevations were not due to a peptide. Thus, the possibility of unextracted naltrexone metabolites remains at least a partial explanation for this apparent FII elevation.

Depressive phenomenology and levels of cerebrospinal fluid endorphins.

Depressive phenomenology and levels of cerebrospinal fluid endorphins.

Chronic administration of ethanol on pituitary and hypothalamic β-endorphin in rats and golden hamsters

The effect of chronic exposure to ethanol on hypothalamic and pituitary endorphin levels of rats and golden hamsters was studied. In rats, chronic ethanol consumption caused a decrease in the level of immuno-reactive (i.r.) β-endorphin (β-EP) in the pituitary but an increase of i.r. β-EP in the hypothalamus. The Met-enkephalin level in the hypothalamus of ethanol-treated rats remained the same as the control. The body weights, as well as food and liquid intake, of ethanol-treated rats were observed to be lower than the controls. In golden hamsters, i.r. β-EP level in the hypothalamus and pituitary remained unchanged with chronic ethanol consumption. The body weight and liquid intake of golden hamsters also remained the same as the controls. Since the changes of pituitary and hypothalamic β-EP after ethanol administration were found only in rats but not in golden hamsters, it is likely that the effects of ethanol observed in rats are not specific.

Endorphin levels in human cerebrospinal fluid during alcohol intoxication and withdrawal.

Levels of endorphins were determined in CSF from alcoholics while intoxicated or after 1 day, 1 week, and 3 weeks of abstinence, respectively, and from healthy volunteers. The level of endorphins was determined by a radioreceptor assay and two fractions were analyzed. With fraction 1, there were no significant differences between the groups, but the level was negatively correlated with the blood-alcohol level. The mean level of endorphin fraction 2 during the early withdrawal phase was significantly lower than those of the other groups. With respect to clinical conditions and monoamine metabolites, fraction 2 in early withdrawal correlated significantly to duration of abuse and age. During late withdrawal, fraction 1 level correlated to depressive symptoms and, after 3 weeks of abstinence, fraction 2 correlated to MOPEG levels. This study suggests that endorphin systems are affected during alcohol intoxication and withdrawal in alcoholics.

Naloxone attenuates the anxiolytic action of diazepam in man

The present study addresses the possible role of endorphins in mediating the anxiolytic properties of diazepam (DZM) in man. The ability of a low dose (0.4 mg. i.v.) of the specific opiate antagonist, Naloxone (NLX) to modify the anxiolytic action of DZM (0.07 mg/kg i.v.) in 22 patients anticipating minor orthopaedic surgery was evaluated. The study was performed in a double-blind placebo (saline)-controlled, randomized design. DZM administered 3 houts pre operation, reduced the anxiety experienced by subjects as estimated on a formal rating scale completed by the patients. NLX, as compared to saline, given 30 min post DZM significantly and strongly attenuated, but did not abolish this effect of DZM. These findings parallel observations in rats of the ability of NLX to block the action of DZM in the conflict test and suggest that the anxiolytic action of DZM in man may be partially mediated by endorphins. A diversity of studies have suggested the benzodiazepines (BZPs) produce their characteristic effects via an enhancement of GABA ergic transmission. Although this apparently represents their primary mechanism of action, other neurotransmitter networks are, evidently, involved in the expression of their effects. Of especial interest in this respect are the endorphins. It was, thus, found that the acute administration of BZPs leads to rapid alterations in the levels of certain endorphins in discrete brain structures (1, 2). Further, although certain actions of BZPs, for example, their discriminative stimulus properties and sedative effects appear to be effected indepentently of endorphins (1, 3, 4), many of the actions of BZPs are moderated by the opiate antagonist, NLX. These include their hypoventilatory, hyperphagic and antinociceptive properties and their ability to facilitate intracranial self-stimulation (1, 5, 6). Of particular interest is the finding, by a number of independent laboratories, that NLX attenuates the anxiolytic activity of BZPs in the conflict test, a method designed for the detection of anxiolytic agents, in animals (1, 5, 6). We have therefore examined the possible role of endorphins as mediators of the anxiolytic actions of BZPs in man.

Endorphin levels in cerebrospinal fluid of patients with postoperative and chronic pain.

The authors measured endorphin levels in the cerebrospinal fluid (CSF) of 12 patients with chronic pain due to lumbar disc syndrome and eight patients with acute postoperative pain. These were compared with CSF endorphin levels in 20 control patients with no history of pain. Endorphins were extracted by adsorption to a synthetic resin (Amberlite XAD-2), eluted with methanol, and assayed using the electrically stimulated mouse vas deferens. Results were expressed as methionine-enkephalin (Met-E) equivalents, which was the standard in the bioassay. The CSF endorphin level was 0.42 +/- 0.07 pmol/ml (mean +/- SE) in the postoperative group, 1.44 +/- 0.2 pmol/ml in the chronic pain group, and 4.36 +/- 0.89 pmol/ml in the control group. CSF endorphin levels in the two pain groups differed significantly from both the control group and each other. These results suggest a correlation between pain levels and endorphin concentration in the CSF; however, in the acute postoperative pain group the influence of other factors such as anesthesia or surgical stress cannot be evaluated.

Endorphins and the modulation of acute pain.

The endorphins constitute a large family of structurally but not generically related peptides. They act pharmacologically like narcotic analgesics. An intimate connection between endorphin fibers and pain pathways is present, for instance, at the spinal level and at the first synapse of primary afferent pain fibers. These fibers may contain the neuropeptide substance P. In acute pain, naloxone injection causes a significant increase in pain suffering. A patient with high preoperative endorphin levels in the cerebrospinal fluid will require less pethidine for adequate pain relief after major abdominal surgery. Pethidine administration reduces substance P levels in the cerebrospinal fluid. The data suggest that endorphins do not have a protective role in acute pain conditions.

Postoperative demand for analgesics in relation to individual levels of endorphins and substance P in cerebrospinal fluid.

Fourteen adult patients were allowed to self-administer small intravenous doses of pethidine to relieve postoperative pain. Thirteen of the patients obtained subjectively satisfactory analgesia while establishing steady-state levels of pethidine in plasma. The individual demand for pethidine was related to individual levels of fraction I endorphins and substance P-like immunoreactivity in the cerebrospinal fluid (CSF). There was a significant and inverse relationship between preoperative fraction I concentrations in CSF and the individual mean pethidine concentrations in plasma (P less than 0.05) and CSF (P less than 0.02) during self-administration. In the 24 h period encompassing surgery and postoperative self-administered analgesia, substance P decreased in 7 patients with calculated CSF pethidine great than 200 ng/ml, but remained virtually unchanged in 7 patients with calculated CSF pethidine less than 200 ng/ml. The results suggest a role for endorphins in the modulation of acute pain and are compatible with experimental evidence for an inhibitory effect of opiates on substance P release.