Major neurotransmitters involved in nociception
Primary afferent nociceptors contain a variety of neurotransmitters, including the excitatory amino acid glutamate and a variety of neuropeptides, such as substance P and CGRP. Glutamate acts upon several subtypes of receptors, including AMPA receptors that mediate a rapid depolarization of dorsal horn neurons, via influx of sodium and efflux of potassium. The N -methyl- d -aspartate (NMDA) receptor, which gates calcium, in addition to sodium and potassium, is involved in noxious stimulus induced long-term changes in dorsal horn processing. Substance P activates subpopulations of dorsal horn neurons and also contributes to some of the long-term changes produced by persistent injury.