Involvement of spinal monoaminergic pathways in antinociception produced by substance P and neurotensin in rodents.

The antinociceptive effects of substance P and of neurotensin have been determined in rodents after depletion of serotonin (5-HT) or noradrenaline (NA) in the spinal cord. The antinociceptive effect of substance P, given intraventricularly, in rats and mice was blocked after depletion of 5-HT in the spinal cord with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or with the inhibitor of the synthesis of 5-HT, p-chlorophenylalanine (PCPA), but not after depletion of NA in the spinal cord with the neurotoxin 6-hydroxydopamine (6-OHDA). Conversely, the antinociceptive effect of neurotensin in mice was blocked after lesion of spinal NA pathways with 6-OHDA. When 5-HT spinal pathways of mice were lesioned with 5,7-DHT, neurotensin-induced antinociception was blocked 7 but not 15 days after the lesion. p-Chlorophenylalanine failed to prevent this effect of neurotensin. The results suggest that the antinociceptive effect of substance P depends on the integrity of spinal 5-HT neurones, whereas that of neurotensin depends on spinal NA neurones and, only to a limited extent, on 5-HT neurones. It seems that different descending systems are involved in the antinociception elicited by these two neuropeptides.