GENDER & OPIOID EFFECTS, INCLUDING ANALGESIA

性别

基本信息

批准号：
6174907
负责人：
JAMES P. ZACNY
金额：
$ 21.94万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-30 至 2001-08-31
项目状态：
已结题

项目摘要

A number of studies have shown differences between males and females in the pain-attenuating or analgesic effects of opioid drugs. In most of the animal studies, males achieved greater opioid-induced analgesia than did females. Of the three studies systematically examining gender and opioid analgesia in humans, there appears to be a gender difference except that it is in the opposite direction to that in animals: females achieve greater analgesia from opioids than do males. The effect appears to be specific to those opioids that have significant agonist activity at the kappa receptor, in that morphine, a full mu agonist, resulted in equivalent degrees of analgesia in males and females. These human studies are an excellent start for addressing an issue of clear clinical importance: the role of gender in opioid analgesia. It may be the case that females in pain would receive better analgesia from some opioids as opposed to others. However, such a notion is premature at this point, since the three studies used only single doses of drug, studied only one full mu agonist, and examined only one type of pain. In this grant application the investigators propose to conduct a behavioral analysis of opioid pharmacodynamics in order to characterize the potential modulating role of gender in opioid effects. The primary endpoint will be analgesia, but other variables will be tested as well, including mood and psychomotor performance. In two studies, healthy volunteers will be exposed to either full mu agonist (Study 1) or mixed agonist-antagonist (Study 2) opioids. A cumulative dosing procedure will be used so that multiple doses of each opioid will be tested, and two pain assays will be employed to induce cold and pressure pain. From the results of these two studies, the following questions (specific aims) can be addressed: a) Is there a gender difference in humans in opioid- induced analgesia? b) Is the gender difference as likely to occur with full mu agonists as with mixed agonist-antagonists? c) Within the class of full mu agonists and within the class of mixed agonist-antagonist drugs that have substantial kappa agonist activity are there uniform gender differences or do gender differences depend on the particular drug, and/or dose of drug within a class being tested? d) If there is a gender difference is it modulated by the type of pain being administered? e) If there is a gender difference, is it manifested in magnitude (peak) of drug effect or in duration of drug effect, or both? and f) If there is a gender effect, is it specific to the behavioral endpoint of analgesia or is it a generalized phenomenon that cuts across other variables such as mood and psychomotor/cognitive performance?

许多研究表明，男性和女性之间的差异阿片类药物的疼痛衰减或镇痛作用。在大多数动物研究，男性获得了比女性。在三项研究中，有系统地检查性别和人类的阿片类镇痛，似乎存在性别差异除了它与动物相反的方向：女性从阿片类药物中获得比男性更大的镇痛。效果似乎特定于那些具有重要激动剂的阿片类药物在Kappa受体中的活性，在该吗啡中，一个完整的MU激动剂，导致男性和女性的镇痛度等效程度。这些人类研究是解决清晰问题的绝佳开始临床重要性：性别在阿片类镇痛中的作用。可能是疼痛中的女性会从某些人那里得到更好的镇痛阿片类药物与他人相反。但是，这样的概念还为时过早这一点，由于这三项研究仅使用了单剂量的药物，所以仅研究了一种完整的MU激动剂，只检查了一种类型的疼痛。在此赠款申请中，调查人员建议进行阿片类药效学的行为分析以表征性别在阿片类药物作用中的潜在调节作用。主要端点将是镇痛，但其他变量也将被测试，包括心情和心理运动表现。在两项研究中，健康志愿者将暴露于完整的MU激动剂（研究1）或混合激动剂 - 抗逆邦剂（研究2）阿片类药物。累积给药程序将使用以使每种阿片类药物的多种剂量被测试，并且两个疼痛测定将用于诱发寒冷和压力疼痛。来自这两项研究的结果，以下问题（具体目的）可以解决：a）阿片类药物的人类性别差异是否存在诱发镇痛？ b）性别差异是否与与混合的激动剂抗逆邦师一样，完整的mu激动剂？ c）在班上完整的MU激动剂和混合激动剂 - 抗抗激师的类别具有重大喀巴激动剂活性的药物均匀性别差异或性别差异取决于特定药物和/或剂量在接受测试的类中？ d）如果有性别差异是它因疼痛的类型而调节管理？ e）如果有性别差异，是否表现出来药物作用的大小（峰）或药物作用的持续时间，还是两者兼而有之？ f）如果有性别效应，它是否特定于行为镇痛的终点，还是一种普遍的现象其他变量，例如情绪和精神运动/认知表现？