Noradrenergic-serotonergic interactions and nociception in the rat.

Spinal noradrenaline (NA) depletion in rats, via either systemic N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) or intrathecal 6-hydroxydopamine (6-OHDA), reversed and/or abolished the analgesic effects of the 5-hydroxytryptamine (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and p-chloroamphetamine (PCA), in shock titration, hot-plate and tail-flick measures of pain sensitivity. Spinal NA depletion also abolished the analgesic effects of 5-HT itself, administered intrathecally, in all three nociception tests and potentiated the analgesic effects of intrathecal NA, a demonstration of receptor supersensitivity. Spinal 5-HT depletion, via intrathecal 5,7-dihydroxytryptamine (5,7-DHT), only attenuated 5-MeODMT-induced analgesia in the tail-flick test but potentiated the 5-MeODMT effect in the hot-plate test. Intrathecal 5,7-DHT treatment caused a drastic potentiation of NA-induced analgesia in the shock titration and tail-flick tests but not in the hot-plate test. Biochemical analyses confirmed the NA and 5-HT depletion. The spinal noradrenergic system appears to be an important tonic factor modulating the function of the descending 5-hydroxytryptaminergic pathway.