Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord

Glutamate, the major excitatory neurotransmitter in the central nervous sys tem, activates three different receptors that directly gate ion channels, n amely receptors for AMPA (alpha-amino-3-hydroxy-5-methyl isoxozole propioni c acid), NMDA (N-methyl-D-aspartate), and kainate, a structural analogue of glutamate. The contribution of AMPA and NMDA receptors to synaptic transmi ssion and plasticity is well established(1). Recent work on the physiologic al function of kainate receptors has focused on the hippocampus(2), where r epetitive activation of the mossy-fibre pathway generates a slow, kainate-r eceptor-mediated excitatory postsynaptic current (EPSC)(3-5). Here we show that high-intensity single-shock stimulation (of duration 200 microseconds) of primary afferent sensory fibres produces a fast, kainate-receptor-media ted EPSC in the superficial dorsal horn of the spinal cord. Activation of l ow-threshold afferent fibres generates typical AMPA-receptor-mediated EPSCs only, indicating that kainate receptors may be restricted to synapses form ed by high-threshold nociceptive (pain-sensing) and thermoreceptive primary afferent fibres. Consistent with this possibility, kainate-receptor-mediat ed EPSCs are blocked by the analgesic mu-opiate-receptor agonist Damgo and spinal blockade of both kainate and AMPA receptors produces antinociception , Thus, spinal kainate receptors contribute to transmission of somatosensor y inputs from the periphery to the brain.