NONSTEROIDAL ANTIINFLAMMATORY DRUG MODULATION OF BEHAVIORAL-RESPONSESTO INTRATHECAL N-METHYL-D-ASPARTATE, BUT NOT TO SUBSTANCE-P AND AMINO-METHYL-ISOXAZOLE-PROPIONIC ACID IN THE RAT

Antinociception by nonsteroidal antiinflammatory drugs, notably diclof enac and S(+)-ibuprofen, has traditionally been attributed to peripher al tissue cyclooxygenase inhibition. This study investigates the poten tial role of the nitric oxide system for the central antinociceptive e ffects of diclofenac, S(+)-, and R(-)-ibuprofen. Diclofenac and S(+)- but not R(-)-ibuprofen inhibited the behavioral response dose dependen tly, ''biting, scratching, and licking (BSL),'' induced by the spinal application of N-methyl-D-aspartate, but not that of amino-methylisoxa zole-propionic acid or substance P. Diclofenac and S(+)-ibuprofen indu ced a parallel shift in the number of BSL responses and in the duratio n of the response in the behavioral model at their approximate median effective doses (diclofenac 1 mu mol and S(+)-ibuprofen 5 mu mol). Pre treatment with L-arginine, the natural substrate for the nitric oxide synthetase, antagonized diclofenac, and S(+)-ibuprofen-induced suppres sion of the biting, scratching, and licking response evoked by intrath ecal N-methyl-D-aspartate. D-arginine did not antagonize the diclofena c- and S(+)-ibuprofen-induced antinociception. The study results indic ate that analgesia after diclofenac and S(+)-ibuprofen involves a cent ral mechanism which may add to the peripheral antinociceptive effect o f these agents. The central action of diclofenac and S(+)-ibuprofen is partly mediated by on interaction with the N-methyl-D-aspartate recep tor and nitric oxide-generating mechanisms.