Prolonged ovarian sex steroid treatment of male rats produces antinociception: identification of sex-based divergent analgesic mechanisms

Simulation of the pregnancy blood concentration profile of 17 alpha-estradi ol (E-2) and progesterone (P) in nonpregnant ovariectomized rats has been s hown to result in a significant elevation of nociceptive response threshold s. The present report demonstrates that spinal opioid antinociceptive respo nsiveness to these ovarian steroids is not sex-specific. Treatment of orchi dectomized sexually mature males with an analogous regimen of E-2 and P als o elicits an antinociception, the robustness and temporal profile of which is comparable with that previously observed in females. Neither E-2 nor P, alone, is sufficient to produce antinociception in male rats, as was previo usly demonstrated in females. Neurobiological substrates and antinociceptiv e mechanisms underlying ovarian sex steroid antinociception do, however, ex hibit sex specificity. In males, the analgesia resulting from ovarian stero id treatment derives from the independent contributions of spinal kappa and mu, not delta, opioid receptor pathways that are additive, not synergistic . Spinal alpha(2)-noradrenergic receptor activity and its attendant analges ic synergy with spinal opioid systems do not contribute to ovarian sex ster oid analgesia in males. This is in contrast to the previous demonstrations that ovarian sex steroid-induced antinociception in females results from an tinociceptive synergy between activated spinal kappa/delta opioid as well, as alpha(2)-noradrenergic receptor systems. The current data reveal that ov arian steroid-activated multiplicative spinal antinociceptive pathways that had been demonstrated in female rats are not manifest in their male counte rparts. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.