Substance P N-terminus inhibits C-fiber-dependent facilitation of the rat flexor reflex

Substance P injected intrathecally or a conditioning stimulus (1 Hz, 20 s) at C-fiber strength, which releases substance P from intraspinal primary afferent terminals, each enhance the hamstring muscle flexor reflex elicited by electrical stimulation of the sural nerve in decerebrate, spinalized rats. This suggests a role for substance P in pain transmission. Since substance P N-terminal metabolites are biologically active, we examined the effect of the metabolite substance P-(1-7) on the flexor reflex and the enhancement of the flexor reflex following a conditioning stimulus of the sural nerve. In contrast to the excitatory effect of substance P, intrathecal injection of substance P-(1-7) had no effect on the flexor reflex. However, 10 and 30 min after injection, 0.6 or 6 micrograms of substance P-(1-7) attenuated the facilitation of the flexor reflex by the conditioning stimulus. These data indicate that substance P-(1-7) may modulate the expression of nociception involving repetitive firing of C-fibers while having no significant effect on acute or phasic responses.