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.
Naranjo
J R
JR
Department of Neuropharmacology, Cajal Institute, CSIC, Madrid, Spain.
Arnedo
A
A
Molinero
M T
MT
Del Rio
J
J
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D004594:Electrophysiology; D010134:Fenclonine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009434:Neural Pathways / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D000700:Analgesics; D015306:Biogenic Monoamines; D006892:Hydroxydopamines; D015116:5,7-Dihydroxytryptamine; D013373:Substance P; D009496:Neurotensin; D016627:Oxidopamine; D010134:Fenclonine; D009638:Norepinephrine