Dual action of substance P in nociception and pain modulation at spinal level.

In the present study, the activation of the nociceptive dorsal horn neurons in rats by iontophoretic substance P (SP) has been observed. Thus, the role of SP in spinal nociception is further identified. In addition, the inhibitory effects of iontophoretic SP on nociceptive response (C response) of dorsal horn neurons can also be observed even in rats that have undergone dorsal half transection of spinal cord. These inhibitory effects can be partially blocked by pretreatment with iontophoretic bicuculline but not by naloxone. It indicates that the SP-induced inhibitory effects on the nociceptive response may be mainly mediated by the presynaptic inhibition in which gamma-aminobutyric acid (GABA) may be involved. In view of the fact that the inhibitory effect of stimulation of nucleus raphe magnus (NRM) on the nociceptive response of dorsal horn neurons in rats depleted of 5-HT with parachlorophenylalanine (pCPA) can be significantly blocked by iontophoretic SP-antagonist, it is supposed that SP may be involved in descending modulation on spinal pain transmission.