Sex-related differences in the antinociceptive effects of opioids:: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the μ opioid receptor
Sex-related differences in the antinociceptive effects of opioids:: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the μ opioid receptor
复制标题
DOI：
10.1007/s002130000453
复制
发表时间：
2000-07-01
影响因子：
3.4
通讯作者：
Picker, MJ
中科院分区：
文献类型：
--
作者：
Cook, CD;Barrett, AC;Picker, MJ
理由：最近的研究表明，吗啡作为一种抗伤害剂，在雄性啮齿动物和猴子中比在雌性啮齿动物和猴子中更有效。目的：评价性别、伤害性刺激强度和阿片类药物对阿片类药物诱导的大鼠品系（F344和刘易斯）镇痛作用的影响，这两种品系对吗啡镇痛作用表现出不同的敏感性。方法：使用大鼠温水（50-56摄氏度）尾部撤回程序进行抗伤害性测试。用各种阿片类药物进行剂量反应和时间过程测定。结果如下：在测试的伤害性刺激强度中，高效μ阿片类药物吗啡、埃托啡和左啡诺在男性和女性中同样有效，但在男性中平均有效2.5倍。在中等刺激强度下，低功效μ阿片类丁丙诺啡在男性中的效力约为0.4倍，并且在较高刺激强度下，在男性中更明显和有效（更大的最大效应）。在低刺激强度下，低功效μ阿片类药物马诺辛和μ/κ阿片类药物布托啡诺在雄性中的效力大于8.9倍，在中等刺激强度下，在雄性中的效力和有效性更高。在低刺激强度下，mu/kappa阿片样物质纳布啡在男性中更有效。在刺激强度，丁丙诺啡，马诺辛，布托啡诺，纳布啡在男性中产生最大的影响，但不是女性，这些阿片类药物拮抗吗啡在女性中的作用。注意到基因型相关差异，因为阿片类药物在F344中的效力通常高于刘易斯雄性，而在F344和刘易斯雌性之间未观察到一致的差异。结论：阿片类药物的效力和有效性的性别差异随着阿片类药物相对效力的降低和伤害性刺激强度的增加而增加，这表明μ阿片类药物作为抗伤害性药物的相对效力在雄性大鼠中大于雌性大鼠。
Rationale: Recent studies indicate that morphine is more potent as an antinociceptive agent in male than female rodents and monkeys. Objectives: To evaluate the influence of sex, nociceptive stimulus intensity and an opioid's relative efficacy on opioid-induced antinotiception in rat strains (F344 and Lewis) that display differential sensitivity to morphine antinociception. Methods: Antinociceptive testing was conducted using a rat warm-water (50-56 degrees C) tail-withdrawal procedure. Dose-response and time-course determinations were performed with various opioids. Results: Across the nociceptive stimulus intensities tested, the high-efficacy mu opioids morphine, etorphine, and levorphanol were equally effective in males and females, but on average 2.5-fold more potent in males. At moderate stimulus intensities, the low-efficacy mu opioid buprenorphine was approximately 0.4-fold more potent in males, and at higher stimulus intensities more patent and effective (greater maximal effect) in males. At low stimulus intensities, the low-efficacy mu opioid dezocine and the mu/kappa opioid butorphanol were greater than 8.9-fold more potent in males, and at moderate stimulus intensities were more potent and effective in males. At a low stimulus intensity, the mu/kappa opioid nalbuphine was more potent and effective in males. At stimulus intensities in which buprenorphine, dezocine, butorphanol, and nalbuphine produced maximal effects in males but not females, these opioids antagonized the effects of morphine in females. Genotype-related differences were noted as opioids were generally more potent in F344 than Lewis males, whereas no consistent differences were observed between F344 and Lewis females. Conclusions: That sex differences in the potency and effectiveness of opioids increased with decreases in the opioid's relative efficacy and with increases in the nociceptive stimulus intensity suggests that the relative efficacy of mu opioids as antinociceptive agents is greater in male than female rats.