PAG mu opioid receptor activation underlies sex differences in morphine antinociception
PAG mu opioid receptor activation underlies sex differences in morphine antinociception
复制标题
DOI：
10.1016/j.bbr.2006.10.028
复制
发表时间：
2007-02-12
影响因子：
2.7
通讯作者：
Craft, Rebecca M.
中科院分区：
文献类型：
--
作者：
Bernal, Scott A.;Morgan, Michael M.;Craft, Rebecca M.
考虑到（1）女性的全身阿片类镇痛作用随动情阶段而变化，以及（2）阿片类镇痛作用的性别差异程度与阿片激动剂疗效呈负相关，我们假设下行疼痛调节系统功能的性别差异可能受女性动情阶段和其中可用阿片受体数量的影响。本研究通过（1）比较吗啡显微注射产生的抗伤害性感受与雌性动物在发情周期不同阶段的腹侧导水管周围灰质（vPAG），以及（2）在vPAG μ阿片受体可用性降低的条件下，检查雄性与雌性动物的全身吗啡抗伤害性感受来验证这些假设。当雌性动物的发情期不受控制时（实验1），在吗啡微量注射（0.3-10 μ g）后，尾部撤回抗伤害感受没有显著的性别差异，尽管吗啡在雄性动物中比雌性动物更有效地产生不动性。实验2表明，vPAG内吗啡在发情期产生的镇痛作用和不动性低于间情期雌性;也就是说，只有发情期雌性对吗啡的反应低于雄性。实验3表明，微量注射不可逆的μ阿片拮抗剂β-funalcidamine（β-FNA）到vPAG中的全身吗啡量效曲线进一步向右移动，在女性比男性。也就是说，可用vPAG mu阿片受体的减少对女性阿片类镇痛作用的影响大于男性，表明女性的vPAG mu阿片受体少于男性。总体而言，这些数据表明，卵巢激素和PAG μ阿片受体密度有助于吗啡产生的抗伤害感受的性别差异。(c)2006 Elsevier B. V.保留所有权利。
Given the findings that (1) systemic opioid antinociception varies by estrous stage in females and (2) the magnitude of sex differences in opioid antinociception is negatively correlated with opioid agonist efficacy, we hypothesized that sex differences in the function of the descending pain modulatory system are likely influenced by estrous stage in females and by the number of available opioid receptors therein. The present study tested these hypotheses by (1) comparing antinociception produced by morphine microinjection to the ventral periaqueductal gray (vPAG) in females at different stages of the estrous cycle and (2) examining systemic morphine antinociception in males versus females under conditions of reduced vPAG mu opioid receptor availability. When estrous stage of females was not controlled for (Experiment 1), there was no significant sex difference in tail withdrawal antinociception following morphine microinjection (0.3-10 mu g), although morphine was more potent in males than females in producing immobility. Experiment 2 showed that intra-vPAG morphine produced less antinociception and immobility in estrus than in diestrus females; that is, only estrus females' response to morphine was lower than that of males. Experiment 3 showed that microinjection of the irreversible mu opioid antagonist beta-funaltrexamine (beta-FNA) into the vPAG shifted the systemic morphine dose-effect curve farther to the right in females than in males. That is, a reduction in available vPAG mu opioid receptors had a greater impact on opioid antinociception in females than in males, suggesting that females have fewer vPAG mu opioid receptors than males. Overall, these data suggest that ovarian hormones and PAG mu opioid receptor density contribute to sex differences in antinociception produced by morphine. (c) 2006 Elsevier B.V. All rights reserved.