Effects of Glutamate Receptor Antagonists on Spinal Dorsal Horn Neurons During Zymosan-Induced Inflammation in Rats

Abstract

These experiments examined the effects of spinal administration of the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV), the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX), or the metabotropic glutamate receptor antagonist DL-2-amino-3-phosphonoproprionic acid (AP3) on responses of spinal dorsal horn neurons evoked by thermal and mechanical stimuli applied to the rat hindpaw in either an inflamed or noninflamed state. Administration of APV, DNQX, or AP3 decreased heat-evoked neuronal discharges of wide dynamic range (WDR) neurons that were previously augmented by zymosan-induced inflammation. APV and DNQX also decreased heat-evoked discharges of WDR neurons that were previously unaffected by saline injection. Administration of either APV or DNQX, but not AP3, decreased heat-evoked neuronal discharges of nociceptive-specific (NS) neurons in both zymosan- and saline-injected rats. These data suggest that NMDA and non-NMDA receptors contribute to spinal processing of thermal stimuli in both the inflamed and noninflamed state, whereas metabotropic glutamate receptors might serve a role that is unique to WDR neurons in the inflamed state. Only DNQX consistently increased mechanical response thresholds and decreased slopes of the mechanical stimulus response functions (SRFs) of NS and WDR neurons, but this effect was observed in both inflamed and noninflamed states. These data suggest that spinal processing of mechanical stimuli is preferentially mediated by glutamate acting at non-NMDA receptors in either the inflamed or noninflamed state.