ANTINOCICEPTIVE ACTIVITY OF INTRATHECAL KETOROLAC IS BLOCKED BY THE KAPPA-OPIOID RECEPTOR ANTAGONIST, NOR-BINALTORPHIMINE

Systemic and intrathecally administered ketorolac produced antinocicep tion in the p-phenylquinone test, but not in the tail-flick or hot-pla te tests. Antagonists of the subtypes of opioid receptors were used to evaluate the interaction of ketorolac with these receptors. Intrathec ally administered kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride blocked the antinociceptive effects of systemic ketor olac and intrathecally administered ketorolac. Naloxone and ICI 174,86 4 failed to block the effects of ketorolac. Activation of nor-binaltor phimine-sensitive receptors appears to be an integral element in the m echanism of antinociception of ketorolac at the spinal level. Ketorola c did not precipitate withdrawal jumping in morphine-tolerant mice dem onstrating that ketorolac does not act as a mixed agonist-antagonist a t the opioid receptor. We suggest that neuraxial placement of ketorola c may prove useful in the clinical setting for the management of acute pain in humans.