The functional role of Ca2+-permeable non-NMDA receptors in spinal nociceptive processing was investigated using joro spider toxin (JSTx), a selective blocker of these receptors. JSTx 0.25 and 1 microg administered spinally produced a significant facilitation of the C-fibre evoked response and post-discharge, but not the A-fibre response, of dorsal horn neurones recorded in adult rats. This may result from a block of Ca2+-permeable AMPA receptors located on GABAergic interneurones. At higher doses, this facilitation of responses was lost, suggesting additional Ca2+-permeable non-NMDA receptors, possibly kainate receptors, in excitatory spinal pathways. Thus, functional Ca2+-permeable AMPA receptors are present within the dorsal horn, predominantly within inhibitory pathways, and play a role distinct from other excitatory amino acid receptors in spinal nociceptive processing.
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