Substance P and calcitonin gene-related peptide synergistically modulate the gain of the nociceptive flexor withdrawal reflex in the rat.

A comparison has been made between the effects of intrathecally administered L-glutamate, L-aspartate, substance P and calcitonin gene-related peptide (CGRP) on the excitability of rat flexor alpha-motoneurons activated monosynaptically by Ia afferents and polysynaptically by high mechano-threshold cutaneous afferents. At doses that do not modify the monosynaptic reflex, substance P, CGRP and some factor released from sural C-fibres increase the excitability of the nociceptive flexion reflex for prolonged periods in a multiplicative fashion. The excitatory amino acids have no such action. We suggest that one role for C-afferent neuropeptides is a long-acting gain modulation of nociceptive inputs into the spinal cord.