Holtman Joseph R, Wala Elzbieta P
Department of Anesthesiology, University of Kentucky, College of Medicine, Chandler Medical Center 800 Rose Street, Lexington KY 40536-0293, USA.
Pharmacol Biochem Behav. 2006 Jan;83(1):100-8. doi: 10.1016/j.pbb.2005.12.013. Epub 2006 Jan 24.
A number of investigators have shown that sex plays an important role in the analgesic effects of opioids. Typically, the antinociceptive responsiveness to mu opioid agonists such as morphine is greater in male than in female rats. The effect of sex on kappa opioid analgesia is less known. The present study was conducted to examine sex-related differences in responsiveness to oxycodone (putative kappa/mu opioid agonist). This information is important since oxycodone is widely used clinically for treatment of pain. The present results indicated that oxycodone had a greater antinociceptive response in female rats compared to male rats. This sex specific responsiveness to oxycodone, however, was lost with chronic administration. The greater antinociception in female rats was even more prominent with U50,488H (selective kappa agonist). Further, low (subanalgesic) doses of oxycodone and U50,488H enhanced the sensitivity to pain (hyperalgesia) to a greater extent in male than in female rats. This is in contrast to the previously shown greater hyperalgesic effect of subanalgesic doses of the mu opioid agonist, morphine, in female than in male rats. The present findings suggest that sexual dimorphism in the effect of opioids is related to the opioid receptors on which they predominately act.
许多研究人员已经表明，性别在阿片类药物的镇痛作用中起着重要作用。通常，雄性大鼠对吗啡等μ阿片受体激动剂的抗伤害感受反应性比雌性大鼠更强。性别对κ阿片受体镇痛作用的影响则鲜为人知。本研究旨在探讨对羟考酮（一种假定的κ/μ阿片受体激动剂）反应性的性别差异。鉴于羟考酮在临床上广泛用于疼痛治疗，该信息具有重要意义。目前的结果表明，与雄性大鼠相比，羟考酮在雌性大鼠中具有更强的抗伤害感受反应。然而，这种对羟考酮的性别特异性反应性在长期给药后消失。U50,488H（选择性κ受体激动剂）在雌性大鼠中产生的更强抗伤害感受作用更为显著。此外，低剂量（亚镇痛剂量）的羟考酮和U50,488H在雄性大鼠中比在雌性大鼠中更大程度地增强了对疼痛的敏感性（痛觉过敏）。这与之前所显示的亚镇痛剂量的μ阿片受体激动剂吗啡在雌性大鼠中比在雄性大鼠中产生更强痛觉过敏效应形成对比。目前的研究结果表明，阿片类药物作用中的性别二态性与它们主要作用的阿片受体有关。
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