Metabotropic glutamate receptor activation contributes to nociceptive reflex activity in the rat spinal cord in vitro.

The contribution of metabotropic glutamate receptor activation to the spinal segmental reflex response evoked at high-intensity electrical stimulation suggesting a role in nociception, has been examined in an in vitro preparation of neonatal rat spinal cord. Segmental reflex responses were recorded as a ventral root depolarization evoked following drug perfusion to the spinal cord or by electrical activation of high-threshold nociceptive afferent fibres. Superfusion of the selective metabotropic glutamate receptor agonist, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], to the spinal cord produced a dose-dependent, reversible ventral root depolarization (EC50 = 58 +/- 7 microM; n = 4), which was antagonized by the selective metabotropic glutamate receptor antagonist, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; IC50 = 243 +/- 61 microM; n = 4). MCPG, over the same concentration range (10 microM-5.0 mM) did not affect N-methyl-D-aspartate-induced ventral root depolarizations. In contrast, the specific N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) reduced N-methyl-D-aspartate-evoked ventral root depolarization but did not affect the depolarization evoked by (1S,3R)-ACPD, thus indicating the specificity of the antagonists for these aggregate responses. MCPG significantly reduced the prolonged phase of the single shock C-fibre-evoked ventral root depolarization (IC50 = 2.9 +/- 0.2 mM; n = 3-5). Low frequency high intensity stimulation of the dorsal root evoked a wind-up response, the amplitude of which was attenuated by both D-AP5 and MCPG in a dose-dependent manner. The ventral root depolarization evoked by capsaicin application (1.0 microM, 30 s) was blocked by both MCPG (IC50 = 809 +/- 35 microM; n = 4) and D-AP5 (IC50 = 143 +/- 43 microM; n = 4). These data suggest that both D-AP5 and MCPG reduced C-fibre-induced ventral root responses. In addition to N-methyl-D-aspartate receptor, metabotropic glutamate receptor activation appears to be involved in the generation of the segmental spinal reflex evoked by high-intensity stimulation in the neonatal rat spinal cord in vitro.