beta-endorphin and Ischemia

The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.

Topics: Aging; Animals; Arousal; beta-Endorphin; Brain; Catecholamines; Hemodynamics; Ischemia; Neuropeptide Y; Pain; Rats; Rats, Inbred SHR; Receptors, Adrenergic, alpha; Receptors, Glucocorticoid; Synapses; Synaptic Membranes; Synaptic Transmission

Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma β-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects.. Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions.. In hierarchical regressions, significant Type (CLBP vs. control)×BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE-related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance.. BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses.

Topics: Administration, Intravesical; Adult; Analgesics, Opioid; beta-Endorphin; Biomarkers; Chronic Pain; Cross-Over Studies; Double-Blind Method; Female; Hot Temperature; Humans; Ischemia; Low Back Pain; Male; Morphine; Pain Measurement; Pain Perception; Regression Analysis; Rest; Sex Characteristics; Treatment Outcome

The anger management styles of anger-in (inhibition) and anger-out (direct expression) are positively associated with pain responsiveness. Opioid blockade studies suggest that hyperalgesic effects of trait anger-out, but not those of trait anger-in, are mediated in part by opioid analgesic system dysfunction. The current study tested the opioid dysfunction hypothesis of anger-out using an alternative index of opioid function: pain-induced changes in plasma endogenous opioids. Plasma beta-endorphin (BE) was assessed at rest and again following exposure to three laboratory acute pain tasks (finger pressure, ischemic, and thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects. As expected, acute pain ratings correlated positively with measures of anger-in (both groups) and anger-out (LBP group; p's<.05). Greater pain-induced increases in BE were associated with significantly lower pain ratings in both groups (p's<.05). Hierarchical multiple regression indicated that greater anger-out significantly predicted smaller pain-induced BE increases (p<.05). Subject type did not moderate this association (p>.10). Anger-in did not display significant main or interaction effects on pain-induced BE changes (p's>.10). The significant association between anger-out and BE release partially mediated the hyperalgesic effects of anger-out on pain unpleasantness, and was not attenuated by statistical control of general negative affect. This suggests unique associations with expressive anger regulation. Elevated trait anger-out therefore appears to be associated with opioid analgesic system dysfunction, whether it is indexed by responses to opioid blockade or by examining circulating endogenous opioid levels. Possible "statextrait" interactions on these anger-related opioid system differences are discussed.

Topics: Acute Disease; Adrenergic alpha-Antagonists; Adult; Anger; beta-Endorphin; Chronic Disease; Female; Hot Temperature; Humans; Ischemia; Low Back Pain; Male; Pain Measurement; Pain Threshold; Pressure; Yohimbine

This study examined gender differences in smoking-related analgesia and stress-induced analgesia (SIA), as a function of pain modality. Forty men (20 smokers, 20 nonsmokers) and 37 women (17 smokers) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests; once following mental stress and once following rest control, counterbalancing order. Cardiovascular and neuroendocrine responses to mental stress were also examined. While expected gender differences in pain sensitivity were observed, women smokers had greater threshold and tolerance times to ischemic pain than women nonsmokers (P<0.05) when pain testing followed rest. Male smokers had greater threshold and tolerance to cold pressor pain than male nonsmokers (P<0.05) after both rest and stress. Only women showed evidence for SIA, since women nonsmokers demonstrated greater ischemic pain threshold and tolerance following mental stress versus rest (P<0.05), and all women reported lower thermal heat pain unpleasantness after stress versus rest (P=0.05). Only nonsmokers showed expected inverse relationships between sympathetic and hypothalamic-pituitary-adrenal (HPA) axis reactivity measures and sensitivity to pain. Smokers showed evidence for blunted HPA-axis function at rest and stress. These results indicate that analgesia related to both being a smoker and stress is influenced by gender and pain modality. The reduced pain perception in smokers and absence of relationships between endogenous pain regulatory mechanisms and pain sensitivity may reflect a maladaptive response to chronic smoking.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Pressure; Cold Temperature; Female; Heart Rate; Hot Temperature; Humans; Hydrocortisone; Ischemia; Male; Nicotine; Nociceptors; Norepinephrine; Pain Threshold; Perception; Sex Characteristics; Smoking; Stress, Psychological; Substance Withdrawal Syndrome

Previously reported differences in sensitivity to experimental pain stimuli between the sexes, as well as between temporomandibular disorder (TMD) patients and healthy control subjects, may be attributable in part to group differences in two pain modulatory mechanisms: the baroreceptor reflex arc and the endogenous opioid system. Twenty-two pain-free (PF) men, 20 PF women and 20 women with TMD underwent two testing sessions in which heat pain and ischemic arm pain threshold and tolerance were measured during both sessions, but followed relaxation during one session and laboratory stress tasks during the other. Blood pressure (BP) and plasma -endorphin (E) concentration were measured during a baseline rest and during the stress or relaxation periods. PF men's threshold and tolerance for heat pain, but not for ischemic pain, exceeded that of PF women's during both sessions. PF women and TMD women did not differ in sensitivity to either pain modality; however, significantly lower ischemic pain threshold (IPTh) was linked to oral contraceptive use in PF women but not TMD patients. In the men alone, higher baseline systolic BP (SBP) was correlated with higher heat pain threshold on both days and heat pain tolerance on the stress day. Conversely, in TMD women, higher baseline SBP was correlated with lower ischemic pain tolerance (IPTol) on both days; BP and pain sensitivity were not related in PF women. In men, but not in PF or TMD women, stress systolic and diastolic BP were positively correlated with heat pain threshold and tolerance and higher diastolic reactivity to stress were correlated with higher heat pain and IPTh and tolerance. On the stress day, higher baseline E level was strongly associated with higher IPTol in PF women but marginally associated with lower IPTol in TMD women. Thus, it appears that a BP-related analgesic mechanism (probably baroreceptor-mediated) predominates in PF men, while an endogenous opioid mechanism predominates in PF women. Stress enhances the expression of these central mechanisms. Female TMDs appear unable to effectively engage normal pain-inhibitory systems; opioid receptor desensitization and/or downregulation are probably implicated, because TMDs' production of E appears normal.

Topics: Adult; Arm; beta-Endorphin; Blood Pressure; Facial Pain; Female; Hot Temperature; Humans; Ischemia; Male; Pain Threshold; Sex Characteristics; Stress, Psychological; Temporomandibular Joint Disorders

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.

Topics: Animals; beta-Endorphin; Dogs; Ischemia; Ligation; Nervous System Diseases; Osmolar Concentration; Spinal Cord

Thirty-six women in their second or third pregnancies were studied in two groups (control and exercise) to determine whether plasma alpha-endorphin levels could be elevated by exercise conditioning during pregnancy. Aerobic training was performed on a bicycle ergometer. Both groups were monitored throughout pregnancy by frequent gynecologic examinations. During labor, both groups of women had pain perception assessment. Blood was sampled for levels of beta-endorphin, cortisol, human growth hormone, and prolactin. Plasma beta-endorphin was found elevated compared to controls in patients who exercised throughout pregnancy. This difference was maintained throughout labor and pain perception during labor was reduced in the patients who exercised. Cortisol, human growth hormone, and prolactin levels were lowered during labor for the exercise-conditioned patients. Exercise conditioning during pregnancy seems to be beneficial in reducing pain perception during labor (as determined by measurement of visual analog pain scales) and in reducing stress levels during labor.

Topics: Arm; beta-Endorphin; Female; Hormones; Humans; Ischemia; Labor, Obstetric; Pain; Pain Measurement; Physical Exertion; Pregnancy; Self Concept; Sensory Thresholds

This paper observed the effect of Dexamethasone (Dex) on the levels of plasma Beta-endorphin-like-immunoreactivity (ir-beta-EP) and its correlation with hemodynamics during the shock. Ten adult mongrel dogs were randomized into two groups. Intestinal shock was created by occluding both superior mesenteric artery and vein in the two groups. After two hours of occlusion, the dogs in treated group were given Dex (5 mg/kg) and the dogs in control group were given normal saline. The intestinal vascular obstruction was released four hours later. It was shown that plasma levels of ir-beta-EP in control group were increased significantly during the shock and correlated significantly with deteriorated hemodynamics. In Dex treated group, the levels of plasma ir-beta-EP and ACTH were significantly lower than that in control group, hemodynamics were improved, and the survival times were much longer. Our results suggest that endogenous opiate beta-EP is involved in the cardiovascular pathophysiology of intestinal shock, and the beneficial effects of steroids (Dex) in the treatment of shock are correlated with its suppressing endogenous beta-EP secretion and release.

Topics: Animals; beta-Endorphin; Dexamethasone; Dogs; Female; Hemodynamics; Intestines; Ischemia; Male; Shock

1. We examined the effect of ischaemic pain and sustained isometric muscle contraction on plasma immunoreactive gamma-lipotropin (gamma LPH), beta-endorphin/beta-lipotropin (beta END/beta LPH) and corticotropin (ACTH), which are all synthesized from a common precursor (pro-opiocortin), and plasma cortisol in 10 normal subjects. 2. Experimental pain was produced by inflation to 250 mmHg of a sphygmomanometer cuff, placed above the elbow of the 'dominant' arm, after which the subject squeezed a hand dynamometer, loaded to 12 kg, 20 times at 2 s intervals. Blood was drawn before, after 5 and 10 min of pain, and 30 min after release of the cuff. In a control session, the subjects were asked to squeeze the handgrip alone for 5 min at 30% of their maximum strength, a procedure which elevates the blood pressure without causing pain. 3. One subject had unexplained high (30--71 pmol/l) baseline peptide concentrations. Baseline values for the nine other subjects were: ACTH, 7.3 +/- 1.9 pmol/l (mean +/- SEM); gamma LPH, 18.6 +/- 1.0 pmol/l; beta END/beta LPH, 10.0 +/- 1.1 pmol/l; cortisol, 599 +/- 55 nmol/l. Neither procedure significantly increased the plasma concentration of ACTH or any other peptide, whereas plasma cortisol was significantly increased at both 5 min and 10 min. Plasma ACTH was positively correlated with plasma gamma LPH (r = 0.701; P less than 0.001), beta END/beta LPH (r = 0.970; P less than 0.001) and plasma cortisol (r = 0.758; P less than 0.05). 4. The present study demonstrates that, in normal man, plasma endorphins do not change with experimental ischaemic pain. The rise in plasma cortisol without concomitant rise in ACTH is not explained, but suggests the action of some other agent at the level of the adrenal cortex.

Topics: Adrenocorticotropic Hormone; Adult; Arm; beta-Endorphin; beta-Lipotropin; Endorphins; Female; Humans; Hydrocortisone; Ischemia; Male; Middle Aged; Pain; Radioimmunoassay; Time Factors