Gestational and ovarian sex steroid antinociception: relevance of uterine afferent and spinal alpha(2)-noradrenergic activity

Pregnancy is associated with an antinociception that is multifactorial and results from spinal (kappa/delta) opioid antinociceptive pathways as well a s peripheral processes (ovarian sex steroids, uterine afferent neurotransmi ssion). The present results provide the first indication that the full mani festation of pregnancy-induced analgesia also requires a supraspinal compon ent. The analgesia of gestation or its hormonal simulation (via estrogen an d progesterone administration; HSP) is substantially attenuated (similar to 60%) following blockade of spinal alpha(2) (but not alpha(1)) adrenergic r eceptors. HSP antinociception is also attenuated by transection of the hypo gastric nerve, the magnitude of which is indistinguishable from that produc ed by spinal alpha(2) receptor blockade. Additionally, hypogastric neurecto my abolishes the component of the antinociception associated with HSP that is mediated by spinal alpha(2) receptors. This suggests that the augmented spinal noradrenergic activity during HSP is not due to activation at the te rminal of noradrenergic spinal projection neurons but requires supraspinal activity. It is suggested that enhanced spinal noradrenergic activity ampli fies ongoing spinal kappa/delta antinociception as has been observed follow ing the concomitant intrathecal application of alpha(2) and opioid agonists . The current observations underscore the importance of visceral afferent a ctivity as well as its modulation by a female-specific hormonal milieu to t he efficacy of endogenous spinal opioid antinociception. (C) 1999 Internati onal Association for the Study of Pain. Published by Elsevier Science B.V.