Naranjo J R, Arnedo A, Molinero M T, Del Rio J
Department of Neuropharmacology, Cajal Institute, CSIC, Madrid, Spain.
Neuropharmacology. 1989 Mar;28(3):291-8. doi: 10.1016/0028-3908(89)90106-8.
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.
在脊髓中5-羟色胺（5-HT）或去甲肾上腺素（NA）耗竭后，已在啮齿动物中测定了P物质和神经降压素的抗伤害感受作用。用神经毒素5,7-二羟基色胺（5,7-DHT）或5-HT合成抑制剂对氯苯丙氨酸（PCPA）使大鼠和小鼠脊髓中的5-HT耗竭后，脑室内给予P物质的抗伤害感受作用被阻断，但用神经毒素6-羟基多巴胺（6-OHDA）使脊髓中的NA耗竭后则未被阻断。相反，用6-OHDA损伤小鼠脊髓NA通路后，神经降压素的抗伤害感受作用被阻断。当用5,7-DHT损伤小鼠的5-HT脊髓通路时，神经降压素诱导的抗伤害感受在损伤后7天而非15天被阻断。对氯苯丙氨酸未能阻止神经降压素的这种作用。结果表明，P物质的抗伤害感受作用取决于脊髓5-HT神经元的完整性，而神经降压素的抗伤害感受作用取决于脊髓NA神经元，且仅在有限程度上取决于5-HT神经元。似乎不同的下行系统参与了这两种神经肽引发的抗伤害感受。
