Electrophysiologic studies on the spinal antinociceptive action of kappa opioid agonists in the adult and 21-day-old rat.

The spinal antinociceptive actions of the selective kappa opioid receptor agonists U50488H and U69593 were investigated in anesthetized adult rats and 21-day-old rat pups. Single unit extracellular recordings were made of dorsal horn neurons responding to both innocuous and noxious peripheral stimuli. Mixed effects on neuronal responses were seen after intrathecal administration of lower doses of the kappa agonists but with higher doses selective inhibitions of C fiber-evoked responses were produced by either U50488H or U69593 in both the adult (ED50 420 and 250 micrograms, respectively) and pup (ED50 63 and 13 micrograms, respectively). In the adult intrathecal U50488H similarly inhibited the more prolonged nociceptive response evoked by s.c. formalin. Intravenous U50488H (4 mg/kg) also produced a rapid and selective inhibition of nociceptive responses in the adult rat. Intrathecal administration of the nonselective opiate antagonist naloxone reduced the inhibitions mediated by U50488H and U69593 in the pup and the adult. However, intrathecal norbinaltorphimine, a selective kappa antagonist, only prevented the action of the kappa agonists in the pup and not in the adult. Kappa receptors are reported to be sparse in the adult rat spinal cord so developmental changes in this receptor may be responsible for the differential action of norbinaltorphimine in the rat pup and adult.