THE INVOLVEMENT OF METABOTROPIC GLUTAMATE RECEPTORS IN SENSORY TRANSMISSION IN DORSAL HORN OF THE RAT SPINAL-CORD

The role of metabotropic glutamate receptors in the processing of soma tosensory information was studied in dorsal horn neurons of the rat sp inal cord. Activation of metabotropic glutamate receptors by local ion tophoresis of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid resul ted in an increased response of dorsal horn neurons to ionotropic glut amate receptor agonists (N-methyl-D-aspartate and kainic acid) applied by iontophoresis. Greater amounts of 1S,3R-1-amino-cyclopentane-1,3-d icarboxylic acid, ejected at high iontophoresis currents, directly exc ited dorsal horn neurons. Application of (1S,3R)-1-amino-cyclopentane- 1,3-dicarboxylic acid also led to a significant increase in responses to innocuous (brush, pressure) but not in responses to noxious (pinch, squeeze) mechanical stimulation. The excitatory effects of (1S,3R)-1- amino-cyclopentane-1,3-dicarboxylic acid were selectively blocked by ( S)-4-carboxy-3-hydroxyphenyl-glycine, an antinociceptive phenylglycine derivative which is a selective group I metabotropic glutamate recept or antagonist, confirming the involvement of these receptors. In wide dynamic range neurons, wind-up, the progressive potentiation of C-fibr e-evoked responses during a train of stimuli, was increased by iontoph oretic application of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic ac id or decreased by iontophoresis of (S)-4-carboxy-3-hydroxyphenyl-glyc ine without significant change in the C-fibre input. The results sugge st an interaction between metabotropic and ionotropic glutamate recept ors in spinal dorsal horn neurons. Metabotropic glutamate receptors pr oved to be involved in the frequency-dependent potentiation of C-fibre responses possibly via modulation of ionotropic glutamate receptors. The long-lasting effects of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxy lic acid on wind-up and on responses to peripheral mechanical stimuli strongly support the view that metabotropic glutamate receptors in the se neurons may play a significant role in spinal synaptic plasticity, and therefore, may contribute to the central sensitization during mech anical hyperalgesia. (C) 1997 IBRO. Published by Elsevier Science Ltd.