Lamina I of the spinal cord plays a key role in sensory transmission between afferent activity and the CNS. Studies have shown lamina I neurones to have distinct response properties compared to deep dorsal horn neurotics, but little is known regarding excitatory amino acid mechanisms in their responses. Spinal electrophysiological recordings of lamina I neurones confirmed that the majority of these neurotics (74%) are nociceptive specific (NS) in their responses, of which 18% can be termed polymodal nociceptive (HPC) (13% of the total population). The remainder (26%) were wide dynamic range. Lamina I neurotics had smaller mechanical and heat-evoked responses compared to deeper dorsal horn neurones. The electrically evoked responses were also smaller, with a distinct lack of an NMDA-mediated 'wind-up' effect. NBQX (AMPA receptor antagonist, 0.5, 5, 50 mug/50 mul) produced dose-dependent inhibitions of the electrically evoked neuronal responses, but APV (NMDA receptor antagonist, 50, 100 500 mug/50 RI) had minimal effects on their responses. These results implicate mainly AMPA receptors in the responses of lamina I neurones. Bicuculline (GABA(A) receptor antagonist, 0.5, 5, 50 mug/50 mul) demonstrated a role exerted by GABA(A) receptors in the control of A-delta fibre-mediated mechanical responses in lamina I. Overall, this study describes a high threshold, AMPA receptor possessing population of lamina I neurones, which seem to lack functional NMDA receptors, and are partially controlled by GABA(A) receptor activity. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.