17-Beta-estradiol and progesterone modulate an intrinsic opioid analgesic system

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 thresholds. 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.