Effects of glutamate receptor antagonists on spinal dorsal horn neurons during zymosan-induced inflammation in rats

These experiments examined the effects of spinal administration of the N-me thyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric a cid (APV), the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dion e (DNQX), or the metabotropic glutamate receptor antagonist DL-2-amino-3-ph osphonoproprionic acid (AP3) on responses of spinal dorsal horn neurons evo ked by thermal and mechanical stimuli applied to the rat hindpaw in either an inflamed or noninflamed state. Administration of APV, DNQX, or AP3 decre ased heat-evoked neuronal discharges of wide dynamic: range (WDR) neurons t hat were previously augmented by zymosan-induced inflammation. APV and DNQX also decreased heat-evoked discharges of Won neurons that were previously unaffected by saline injection. Administration of either APV or DNQX, but n ot AP3, decreased heat-evoked neuronal discharges of nociceptive-specific ( NS) neurons in both zymosan- and saline-injected rats. These data suggest t hat NMDA and non-NMDA receptors contribute to spinal processing of thermal stimuli in both the inflamed and noninflamed state, whereas metabotropic gl utamate receptors might serve a role that is unique to Won neurons in the i nflamed state. Only DNQX consistently increased mechanical response thresho lds and decreased slopes of the mechanical stimulus response functions (SRF s) of NS and WDR neurons, but this effect was observed in both inflamed and noninflamed states. These data suggest that spinal processing of mechanica l stimuli is preferentially mediated by glutamate acting at non-NMDA recept ors in either the inflamed or noninflamed state.