Spinal κ-opiate receptor involvement in the analgesia of pregnancy: effects of intrathecal nor-binaltorphimine, a κ-selective antagonist

In a variety of laboratory animals as well as humans, pregnancy has been associated with an activation of a maternal opioid system(s) and with a concomitant elevation in the threshold for maternal responsiveness to aversive stimuli. This analgesia is mediated via the activation of spinal opiate receptors and does not require an intact peripheral opioid system(s). The recently developed κ-selective opioid antagonist, nor-binaltorphimine (nor-BNI), significantly reduces the threshold for reflexive jumping in response to electric foot shock when administered to the lumbar intrathecal (i.t.) space of pregnant rats (day 20 of gestation). In contrast, i.t. nor-BNI when administered to non-pregnant rats as well as systemic (i.p.) administration of an intrathecally effective dose of nor-BNI to pregnant rats is without effect on the jump thresholds. These data indicate that the κ-type of opiate receptor mediates, at least in part, the analgesia observed during gestation, thus providing an important physiological function for this receptor type.