The roles of different types of glutamate receptors involved in the mediation of nucleus submedius (Sm) glutamate-evoked antinociception in the rat.

Based on our previous findings that glutamate microinjected into the thalamic nucleus submedius (Sm) inhibits dose-dependently the rat tail-flick (TF) reflex, this study investigated which glutamate receptor subtype is involved in mediating this effect. The effects of an NMDA (N-methyl-D-aspartate), non-NMDA or metabotropic glutamate receptor (mGluR) antagonist microinjected into Sm on the TF reflex were examined in untreated or in Sm glutamate treated (microinjection into the Sm) rats. The TF latencies were measured in each of these groups of rats every 5 min. Injection of DNQX [6,7-dinitroquinoxaline-2,3(1H,4H)-dione], a non-NMDA receptor antagonist, or (+/-)-MCPG [(+/-)-alpha-methyl-4-carboxyphenylglycine], a mGluR antagonist, into the Sm blocked the inhibitory effects induced by a subsequent microinjection of glutamate into the same Sm site. The TF latency increased only by 6.6+/-1.6 or 9.0+/-1.1%, respectively, of the baseline value, which was markedly less than that (51.3+/-8.4 or 50.7+/-5.3%) obtained from injection of glutamate only (P<0.001, n=8). However, pre-microinjection of MK-801 [(+)-5-methyl-10,11-dibenzo[a,d]cyclohepten-5,10-imine], an NMDA receptor antagonist, into the Sm had no effect on the Sm glutamate-evoked inhibition of the TF reflex. The TF latency change (40.0+/-11.1%) was not significantly different (P>0.05, n=8) compared with that obtained from glutamate injection alone. These observations suggest that non-NMDA and metabotropic glutamate receptors, but not NMDA receptors, are involved in mediating Sm glutamate-evoked antinociception.