Intrathecal substance P modulates the depressant effect of 5-methoxy-N,N-dimethyltryptamine on a reflex response to radiant heat in mice.

The effect of intrathecal (i.th.) substance P (SP) on antinociception elicited by the serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was investigated in mice by means of the tail-flick method. Substance P (0.07, 0.7 or 7 micrograms) induced a behavioral syndrome for 1-2 min, but had no apparent toxic or neurologic effects and did not alter the tail-flick response to noxious radiant heat 30 min after injection. The depressant effect of 5-MeODMT (3 mg/kg) on tail-flick responses was, however, markedly attenuated when administered 30 min after SP. The tail skin temperatures of vehicle- and SP-injected mice were nearly identical 30 min after i.th. injection as well as after administration of 5-MeODMT. The results indicate a functional interaction between SP and 5-HT in spinal nociceptive processes, and it is suggested that i.th. SP modulates the function of 5-HT receptors.