Intramuscular Ketorolac Inhibits Activation of Rat

36 37 The non-steroidal-anti-inflammatory-drug (NSAID) diclofenac has local anesthetic-like 38 and peripheral N-methyl-D-aspartate (NMDA) receptor antagonist characteristics when 39 administered at higher concentrations to masticatory muscle. It is not known if the ability 40 to inhibit NMDA receptors is unique to diclofenac, or is shared by other NSAIDs. This 41 study was undertaken to determine if intramuscular injection of ketorolac or naproxen at 42 concentrations that did not exhibit local anesthetic-like effects could attenuate jaw-closer 43 muscle nociceptor discharge in anesthetized Sprague Dawley rats. It was found that 44 ketorolac (5 mM) inhibited hypertonic saline-evoked nociceptor discharge, which 45 suggests that at this concentration ketorolac has local anesthetic-like properties. A lower 46 concentration of ketorolac (0.5 mM), which did not affect hypertonic saline-evoked 47 discharge, did inhibit nociceptor discharge evoked by NMDA. In contrast, naproxen 48 (5mM) did not alter hypertonic salineor NMDA-evoked nociceptor discharge. 49 Subsequent experiments revealed that ketorolac (0.5 mM) had no effect on nociceptor 50 discharge evoked by α,β-methylene adenosine triphosphate (ATP), 5-hydroxytryptamine 51 or 2-amino-3-(5-methyl-3-oxo-1,2oxazol-4-yl) propanoic acid (AMPA). The inhibitory 52 effect of ketorolac did not appear to be related to cyclooxygenase inhibition, as the 53 concentration of prostaglandin E2 in the masticatory muscles 10 minutes after injection 54 of either NSAID was not significantly decreased. The present study indicates that in 55 vivo, ketorolac, but not naproxen, can antagonize NMDA-evoked nociceptor discharge 56 similar to diclofenac. We speculate that structural similarities between ketorolac and 57 diclofenac could account for the ability of these NSAIDs to inhibit NMDA-evoked 58