17β-Estradiol and Progesterone Positively Modulate Spinal Cord Dynorphin: Relevance to the Analgesia of Pregnancy

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.