Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord

Excitatory amino acid (EAA) receptor agonists were tested for their effect on identified rat spinal neurons. Only 75% of the spinal neurons tested increased their firing rate in response to iontophoretic application of one or more of the EAA receptor agonists, N-methyl-d-aspartate (NMDA), quisqualate (Quis), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid HBr (AMPA), and kainate (KA). NMDA and Quis or AMPA activated primarily nociceptive neurons (60% of these neurons were projection neurons) in the rat spinal cord. KA-activated neurons were primarily classified as low threshold neurons. Both NMDA and AMPA, at subthreshold doses, significantly increased neuronal responses to peripheral noxious mechanical stimulation; NMDA also significantly increased neuronal responses to peripheral noxious thermal stimulation. Iontophoretically applied phencyclidine (PCP) decreased NMDA-induced firing in 100% of the cells tested while Quis-induced firing was blocked by PCP in only 33% of the cells tested. The reported analgesic effects of PCP in humans may result from a spinal action involving its well documented interaction with NMDA receptors.