EVIDENCE THAT SUBSTANCE-P SELECTIVELY MODULATES C-FIBER-EVOKED DISCHARGES OF DORSAL HORN NOCICEPTIVE NEURONS

Previous studies suggest that the undecapeptide substance P (SP) functions as a primary afferent neurotransmitter or neuromodulator of nociception which may mediate the slow temporal summation ('windup') of discharges of dorsal horn nociceptive neurons elicited by repetitive stimulation of C-afferents. The present study tested this hypothesis by investigating the effects of local spinal application of SP and and SP antagonist, [D-Pro2, D-Trp7,9]-SP (DPDT), on A- and C-fiber-evoked firing of dorsal horn neurons in an intact, urethane-anesthetized rat preparation. Extracellular single unit recordings from both wide dynamic range and nociceptive specific neurons during controlled repetitive electrical stimulation of the ipsilateral hind paw indicated that SP enhanced C-evoked firing in an pparent dose-related manner (100 > 20 = 4 nmol), whereas DPDT inhibited C-evoked discharges with an apparent bell-shaped dose-response (20 > 100 = 4 nmol). Neither agent significantly altered either A-evoked or spontaneous activity. In agreement with previous investigators, morphine sulfate also selectively inhibited C-fiber-evoked firing without altering A-fiber-mediated activity, validating the selectivity of our system. These findings provide additional evidence that SP functions as a neuromodulator of primary afferent nociception, and further suggest that the effects of SP are selective to nociceptive transmission mediated by C-fibers. © 1990.