Differential effects of excitatory amino acid antagonists on dorsal horn nociceptive neurones in the rat

Abstract

The effects of two excitatory amino acid receptor antagonists γ- d-glutamylglycine (DGG) and 2-amino-5-phosphonovaleric acid (AP5), applied onto the spinal cord surface, were tested on the responses of dorsal horn nociceptive neurones in the anaesthetized rat. DGG is a non-selective antagonist at both the N-methyl- d-aspartate (NMDA) and non-NMDA receptors, whereas AP5 acid is selective for the NMDA receptor. DGG dose-dependently reduced the A and C fibre-evoked responses of neurones in all laminae of the dorsal horn and also inhibited the post-discharges of intermediate and deep neurones resulting from repeated C fibre stimulation. There was little difference in the effects of the antagonist on the intermediate neuronal population compared to superficial or deep cells in the dorsal horn. AP5 las little effect on C fibre-evoked activity in superficial cells but produced slight inhibitions of the C fibre-evoked responses and clear reductions in the post-discharge of the deep neurones. This contrasts with the excitatory effects of the antagonist on both types of responses in the intermediate cells. A fibre-evoked responses were unaffected by AP5. Taking into account the results with the two antagonists it appears that both A and C fibre-evoked responses of dorsal horn nociceptive neurones are mediated by non-NMDA receptors whilst the C fibre-evoked wind-up of deep dorsal horn cells involves the NMDA receptor which also seems to mediate, in a complex manner, C fibre responses of intermediate, presumed substantia gelatinosa neurones. The results are discussed with regard to nociceptive mechanisms in the dorsal horn.