Antinociceptive activity of intrathecal ketorolac is blocked by the kappa-opioid receptor antagonist, nor-binaltorphimine.
Systemic and intrathecally administered ketorolac produced antinociception in the p-phenylquinone test, but not in the tail-flick or hot-plate tests. Antagonists of the subtypes of opioid receptors were used to evaluate the interaction of ketorolac with these receptors. Intrathecally administered kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride blocked the antinociceptive effects of systemic ketorolac and intrathecally administered ketorolac. Naloxone and ICI 174,864 failed to block the effects of ketorolac. Activation of nor-binaltorphimine-sensitive receptors appears to be an integral element in the mechanism of antinociception of ketorolac at the spinal level. Ketorolac did not precipitate withdrawal jumping in morphine-tolerant mice demonstrating that ketorolac does not act as a mixed agonist-antagonist at the opioid receptor. We suggest that neuraxial placement of ketorolac may prove useful in the clinical setting for the management of acute pain in humans.
Uphouse
L A
LA
Department of Nurse Anesthesia, MCV Station, Richmond 23298-0226.
Welch
S P
SP
Ward
C R
CR
Ellis
E F
EF
Embrey
J P
JP
D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D007278:Injections, Spinal; D020910:Ketorolac; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000700:Analgesics; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; D014046:Tolmetin; D020910:Ketorolac