Analgesic mechanism of neurotropin: relation to the serotonergic system and influence of spinal cord transection.
Neurotropin, a nonprotein component extracted from the skin of rabbits treated with vaccinia virus, has been clinically and experimentally reported to demonstrate analgesic effects. In this study, we investigated the antinociceptive action of neurotropin in relation to the serotonergic system, a pain inhibitory system, and substance P, a pain transmitter; we also attempted to determine whether it acts at the spinal or supraspinal level in mice. 1) The spinal cord (T6-T10) transection completely abolished the antinociceptive action of neurotropin, attenuated that of morphine, and had no influence on the action of clonidine. 2) The intrathecal substance P-induced behavior was inhibited by [D-Pro2, D-Trp7,9]-substance P, but not by neurotropin. 3) Preadministration of p-chlorophenylalanine or cyproheptadine inhibited the antinociceptive action of neurotropin. These data suggest that neurotropin does not directly act on pain transmitters at the spinal cord level, but acts at the supraspinal level, resulting in an inhibition of pain transmitter release at the spinal level by mediating pain inhibitory systems such as the serotonergic system in addition to the noradrenergic and GABAergic systems previously reported.
Itoh
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E
Department of Pharmacology, Faculty of Pharmacy, Kinki University, Higashi-Osaka, Japan.
Hata
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T
D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002946:Cisterna Magna; D003533:Cyproheptadine / Q000494:pharmacology; D003655:Decerebrate State; D010134:Fenclonine / Q000494:pharmacology; D007267:Injections; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000503:physiopathology; D011134:Polysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology
D000700:Analgesics; D011134:Polysaccharides; D011985:Receptors, Serotonin; D003533:Cyproheptadine; D013373:Substance P; C010491:neurotropin; D010134:Fenclonine