N-methyl D-aspartate induced mechanical allodynia is blocked by nitric oxide synthase and cyclooxygenase-2 inhibitors

THE role of spinal NMDA receptors in mechanical nociceptive processing was assessed in sheep. Intrathecal NMDA (2 nmol-1 mu mol) produced a significant reduction in mechanical withdrawal thresholds. This effect was attenuated by pretreatment with the NMDA receptor antagonist MK801 (100 nmol), the cyclooxyoenase-2 (COX-2) inhibitor 5,5-dimethyl-3-(3-flourophenyl)-4-(4-methylsulphonyl)phenyl-2(5H) furanone DFU; 200 nmol) and the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 2 mu mol), but not by the metabotropic glutamate receptor antagonist (S)-alpha-methyl-4-carboxyphenylglycine (MCPG; 200 nmol-2 mu mol) or the non;NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 200 nmol-1 mu mol). This first report of NMDA-induced mechanical allodynia suggests that spinal NMDA receptors are involved in mediating acute mechanical nociceptive processing through activation of NOS and COX-2 enzymes. (C) 1999 Lippincott Williams & Wilkins.