Involvement of spinal cord delta opiate receptors in the antinociception of gestation and its hormonal simulation
Involvement of spinal cord delta opiate receptors in the antinociception of gestation and its hormonal simulation
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DOI：
10.1016/s0006-8993(97)00092-9
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发表时间：
1997-05-16
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, M;Gintzler, AR
生理以及激素模拟妊娠（HSP）与阿片类药物介导的母体伤害阈值升高有关。该实验室以前的报告已经证明脊髓阿片受体参与了这种现象。进行本研究是为了确定这种调解的排他性。鞘内注射（i.t）阿片受体选择性拮抗剂纳曲多（NTI）、7-苄基烯丙曲酮（BNTX）或钠三苯（NTB）可显著降低妊娠期（第20天）和热休克反应（第19天）的伤害阈值。在未怀孕或给药的对照动物中未观察到这些化合物在给药后的致痛觉作用。这些数据表明，三角洲阿片受体活性是一个先决条件的表现，很大一部分妊娠期和热休克镇痛。相比之下，多选择性拮抗剂d - phe - cys - tyr - d - trp - arg - thr - penr - thr - nh2 （CTAP）的应用对妊娠第20天的伤害阈值没有影响，正如之前对热休克蛋白诱导的抗伤害阈值所证明的那样。因此，强效脊髓镇痛系统不参与妊娠期或热休克镇痛。在生理妊娠期间，脊髓内固有阿片镇痛系统（三角洲和kappa阿片系统）中较弱的成分被招募来介导母体妊娠的抗痛觉。此外，雌激素和孕激素调节脊柱阿片类抗痛觉活性的能力强调了男性和女性对止痛药反应的潜在差异。
Physiological as well as hormone-simulated pregnancy (HSP) is associated with opioid-mediated elevations in maternal nociceptive thresholds. Previous reports from this laboratory have demonstrated the involvement of spinal cord kappa opiate receptors in this phenomenon. The present study was undertaken in order to determine the exclusivity of this mediation. Intrathecal (i.t.) administration of the delta opiate receptor-selective antagonists naltrindole (NTI), 7-benzylidenenaltrexone (BNTX) or naltriben (NTB) substantially reduces nociceptive thresholds of gestation (day 20) and HSP (day 19). Hyperalgesic actions of these compounds following i.t. administration are not observed in non-pregnant or vehicle-treated control animals. These data indicate that delta opiate receptor activity is a prerequisite for the manifestation of a substantial portion of gestational and HSP analgesia. In contrast, i.t. application of the mu-selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) has no effect on nociceptive thresholds of gestational day 20, as was previously demonstrated for HSP-induced antinociception. Thus, the potent spinal mu analgesic system does not participate in gestational or HSP analgesia. During physiological pregnancy, less robust constituents of intrinsic opioid pain-attenuating systems in the spinal cord (delta and kappa opioid systems) are recruited to mediate the maternal antinociception of gestation. Furthermore, the ability of estrogen and progesterone to modulate spinal opioid antinociceptive activity emphasizes potential differences between men and women in their response to pain medication.