Involvement of spinal cord delta opiate receptors in the antinociception of gestation and its hormonal simulation.

Physiological as well as hormone-simulated pregnancy (HSP) is associated with opioid-mediated elevations in maternal nociceptive thresholds. Previous reports from this laboratory have demonstrated the involvement of spinal cord kappa opiate receptors in this phenomenon. The present study was undertaken in order to determine the exclusivity of this mediation. Intrathecal (i.t.) administration of the delta opiate receptor-selective antagonists naltrindole (NTI), 7-benzylidenenaltrexone (BNTX) or naltriben (NTB) substantially reduces nociceptive thresholds of gestation (day 20) and HSP (day 19). Hyperalgesic actions of these compounds following i.t. administration are not observed in non-pregnant or vehicle-treated control animals. These data indicate that delta opiate receptor activity is a prerequisite for the manifestation of a substantial portion of gestational and HSP analgesia. In contrast, i.t. application of the micro-selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) has no effect on nociceptive thresholds of gestational day 20, as was previously demonstrated for HSP-induced antinociception. Thus, the potent spinal mu analgesic system does not participate in gestational or HSP analgesia. During physiological pregnancy, less robust constituents of intrinsic opioid pain-attenuating systems in the spinal cord (delta and kappa opioid systems) are recruited to mediate the maternal antinociception of gestation. Furthermore, the ability of estrogen and progesterone to modulate spinal opioid antinociceptive activity emphasizes potential differences between men and women in their response to pain medication.