Medina V M, Dawson-Basoa M E, Gintzler A R
Department of Biochemistry, State University of New York, Health Science Center at Brooklyn 11203.
Neuroendocrinology. 1993 Sep;58(3):310-5. doi: 10.1159/000126555.
Pregnancy and parturition are associated with opioid-mediated elevations in maternal pain thresholds. This analgesia is subserved by a spinal cord dynorphin/kappa-opiate receptor system. During gestation, elevated pain thresholds are paralleled by a significant increase in the content of dynorphin (1-17 and 1-8) in the lumbar spinal cord. An additional increment in lumbar dynorphin (1-17) concentration, but not that of dynorphin (1-8), occurs in parturient animals. Simulation of the pregnancy blood concentration profile of 17 beta-estradiol and progesterone ('hormone-simulated pregnancy') also results in an opioid analgesia, the magnitude and temporal pattern of which closely approximates that of actual gestation. The current study demonstrates that during hormone-simulated pregnancy, the spinal cord content of dynorphin (1-17) [but not dynorphin (1-8)] is positively modulated. This regulation is time- (or dose-)-dependent and region-specific. Significant elevations in spinal levels of dynorphin (1-17) are observed during steroid dose periods 3 and 4, corresponding to the last week of actual gestation and parturition, respectively. Increased dynorphin (1-17) content is observed in only the lumbar spinal region. These changes are temporally and anatomically identical to those which occur during actual gestation and parturition. It is concluded that changes in circulating 17 beta-estradiol and progesterone, that occur as a natural consequence of gestation, activate a dynorphin system in the lumbar spinal cord. This attenuates the pain associated with late pregnancy and labor. The pattern of circulating sex steroids can be an important determinant of the activity of central opioid analgesic systems.
妊娠和分娩与阿片类物质介导的母体痛阈升高有关。这种镇痛作用由脊髓强啡肽/κ-阿片受体系统介导。在妊娠期，痛阈升高的同时，腰段脊髓中强啡肽（1-17和1-8）的含量显著增加。在分娩动物中，腰段强啡肽（1-17）的浓度进一步升高，但强啡肽（1-8）的浓度没有变化。模拟17β-雌二醇和孕酮的妊娠血药浓度曲线（“激素模拟妊娠”）也会产生阿片类镇痛作用，其强度和时间模式与实际妊娠非常相似。本研究表明，在激素模拟妊娠期间，脊髓中强啡肽（1-17）[而非强啡肽（1-8）]的含量受到正向调节。这种调节是时间（或剂量）依赖性的，且具有区域特异性。在类固醇剂量期3和4期间，观察到脊髓中强啡肽（1-17）水平显著升高，分别对应于实际妊娠的最后一周和分娩期。仅在腰段脊髓区域观察到强啡肽（1-17）含量增加。这些变化在时间和解剖学上与实际妊娠和分娩期间发生的变化相同。研究得出结论，妊娠过程中循环的17β-雌二醇和孕酮的变化激活了腰段脊髓中的强啡肽系统。这减轻了与晚期妊娠和分娩相关的疼痛。循环性类固醇的模式可能是中枢阿片类镇痛系统活性的重要决定因素。
