17-BETA-ESTRADIOL AND PROGESTERONE MODULATE AN INTRINSIC OPIOID ANALGESIC SYSTEM
17-BETA-ESTRADIOL AND PROGESTERONE MODULATE AN INTRINSIC OPIOID ANALGESIC SYSTEM
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DOI：
10.1016/0006-8993(93)91716-6
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发表时间：
1993-01-22
期刊：
影响因子：
2.9
通讯作者：
GINTZLER, AR
中科院分区：
文献类型：
--
作者：
DAWSONBASOA, MB;GINTZLER, AR
在大鼠和人类中已经证明，怀孕和分娩与阿片类药物介导的母体镇痛有关。这种镇痛已被证明涉及脊髓运动啡/kappa-阿片系统。在本研究中，对未怀孕、切除卵巢的大鼠的妊娠血液中17- β -雌二醇（E2）和孕酮(P)的模拟结果显示，疼痛阈值有统计学意义的升高。这种镇痛的时间模式和强度与实际妊娠期间观察到的惊人相似。单独给予妊娠期水平的E2或P或E2与延迟添加P（从剂量3开始，即开始镇痛的剂量）都不足以产生疼痛阈值的增加。因此，整个妊娠过程中类固醇激素的作用是导致镇痛的表现。慢性给药麻醉拮抗剂纳曲酮阻断了与激素模拟妊娠相关的痛阈增加，表明它是通过内源性阿片系统介导的，就像实际妊娠的镇痛一样。激素模拟妊娠镇痛与实际妊娠镇痛之间惊人的相似性强烈表明，血浆E2和P的变化谱是妊娠状态的一个参数，对疼痛阈值升高的表现至关重要。这些数据也表明存在一个阿片类镇痛系统，受卵巢性类固醇调节。
It has been demonstrated in rats as well as in humans, that pregnancy and parturition are associated with an opioid-mediated maternal analgesia. This analgesia has been shown to involve a spinal cord dynorphin/kappa-opioid system. In the present study, simulation of the pregnancy blood profile of 17-beta-estradiol (E2) and progesterone (P) in non-pregnant, ovariectomized rats resulted in a statistically significant elevation in pain threshoids. The temporal pattern and magnitude of this analgesia was strikingly similar to that which has been observed during actual gestation. Administration of pregnancy levels of either E2 or P alone or E2 with the delayed addition of P (starting with dose 3, the dose at which the onset of analgesia occurred) was not sufficient to produce the increase in pain threshold. Therefore, the entire pregnancy profile of steroid hormones is responsible for the manifestation of analgesia. Chronic administration of the narcotic antagonist naltrexone blocked the increase in pain threshold associated with hormone-simulated pregnancy, indicating that it is mediated via an endogenous opioid system(s), as is the analgesia of actual pregnancy. The striking similarities between the analgesia of hormone-simulated pregnancy and actual gestation strongly suggest that the profile of change in plasma E2 and P is a parameter of the pregnant condition essential for the manifestation of elevated pain thresholds. These data also indicate the existence of an opioid analgesic system that is subject to modulation by ovarian sex steroids.