Activation of brainstem metabotropic glutamate receptors inhibits spinal nociception in adult rats

In this study, we provide evidence that focal electrical stimulation applied to the rostroventral medulla (RVM) at a high frequency (100 Hz) produced inhibition of the spinal nociceptive tail-flick (TF) reflex in lightly anesthetized adult rats. Chemical activation of metabotropic glutamate (mGlu) receptors by local injection of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD), the mGlu receptor agonist, produced a dose-related inhibition of the TF reflex. Injection of the Group H mGlu receptor agonist (2S,2'R,3'R)-2-(2,3'-dicarboxycyclopropyl) glycine (DCGIV) produced strong inhibition, while injection of the Group III mGlu receptor agonist L(+)-2amino-4-phosphonobutyric acid (L-AP4) did not produce any effect. (RS)-alpha-Methyl-4-carboxyphenylglycine (MCPG), a selective mGlu receptor antagonist, but not naloxone reversed the inhibitory effects of DCGIV. Our results provide physiological evidence in vivo that activation of Group 11 mGlu receptors in the brainstem is antinociceptive and drugs targetting these receptors may help to control pain in humans. (C) 2002 Elsevier Science Inc. All rights reserved.