Is substance P a primary afferent neurotransmitter for nociceptive input? IV. 2-Amino-5-phosphonovalerate (APV) and [D-Pro2,D-Trp7,9]-substance P exert different effects on behaviors induced by intrathecal substance P, strychnine and kainic acid.

Intrathecal (i.t.) pretreatment with 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, diminished scratching with the hindlimbs, vocalization, biting or licking, and myoclonic twitches produced by i.t. strychnine, kainic acid, or morphine in rats. APV did not diminish these behaviors when produced by i.t. substance P (SP). The SP analogue [D-Pro2,D-Trp7,9]-substance P (DPDT) failed to affect any behaviors produced by all of these compounds at non-paralytic doses. At these doses, neither APV nor DPDT changed the thermal and mechanical pain thresholds. These results indicate that SP does not produce scratching at the primary afferent synapse in the spinal cord, that hindlimb scratching in rats is neither necessary nor sufficient to infer the presence of pain in rats, and that SP may not be involved uniquely, if at all, in the transmission of nociceptive information at the primary afferent synapse.