Involvement of Spinal NMDA Receptors in Capsaicin-Induced Nociception

Abstract

SAKURADA T., K. WAKO, A. SUGIYAMA, C. SAKURADA, K. TAN-NO AND K. KISARA. Involvement of spinal NMDA receptors in capsaicin-induced nociception. PHARMACOL BIOCHEM BEHAV 59(2) 339–345, 1998.—Intraplantar injection of capsaicin into the mouse hindpaw produced an acute nociceptive response. The involvement of N-methyl- d-aspartate (NMDA) receptors was examined by intrathecal administration of various excitatory amino acid (EAA) receptor antagonists. The selective and competitive NMDA receptor antagonists, d(−)-2-amino-5-phosphono-valeric acid (APV) and (±)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphoric acid (CPP), were most potent in inhibiting the nociceptive response induced by capsaicin (ED 50, 0.23 nmol and 0.12 nmol). The noncompetitive NMDA receptor antagonist dizocilpine (MK-801) and the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had similar effects on the capsaicin-induced nociception (ED 50, 2.90 and 7.98 nmol), while ketamine and 7-chlorokynurenic acid were without effect. Ifenprodil, an antagonist at the receptor-coupled polyamine site, showed a significant reduction of the nociceptive response (ED 50, 13.8 nmol). The inhibitory effects of APV, CPP, MK-801, and ifenprodil were reversed by co-administration of NMDA. Coadministration of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainate resulted in a marked reduction of CNQX-induced antinociception. The present results suggest that the NMDA receptor plays a key role in spinal nociceptive processing as measured by the capsaicin test in mice. This nociceptive test may be useful for evaluating competitive NMDA antagonists.