Evidence for an involvement of tachykinins in allodynia in streptozocin-induced diabetic rats.
A better knowledge of the pathophysiology of chronic pain could help to improve the treatment of patients with such syndrome. The aim of the present work was to elucidate the possible involvement of spinal substance P and neurokinin A in the mechanical and thermal allodynia observed in streptozocin-induced diabetic rats. A tachykinin NK(1) receptor antagonist, RP-67,580 ((3aR,7aR) -7, 7-diphenyl-2-(1-imino-2(2-methoxy phenyl)-ethyl) perhydroisoindol-4-one hydrochloride), a tachykinin NK(2) receptor antagonist, SR-48,968 ((S)-N-methyl (4-(acetylamino-4phenylpiperidino)-2-(3, 4-dichlorophenyl) butyl) benzamide) and their respective enantiomers were intrathecally administered 4 weeks after the induction of diabetes. Mechanical and thermal allodynia were evaluated before and up to 60 min after injection. The tachykinin receptor antagonists at the highest doses (10 and 25 microgram) significantly reduced allodynia, their enantiomers being inactive. Both of these data suggest the involvement of substance P and neurokinin A in the neuropathy-induced allodynia and offer a novel hypothesis to treat chronic pain due to diabetes.
Laboratoire de Physiologie, Faculté de Pharmacie, Equipe NPPUA (EA 1741, EPI HU 9904 INSERM), 28 Place Henri Dunant, BP 38, 63001 Cedex 1, Clermont-Ferrand, France. m-ange.coudore@u-clermont1.fr
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M
Coudoré-Civiale
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Courteix
M
M
Boucher
J
J
Fialip
A
A
Eschalier
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000502:physiology*; D013696:Temperature; D013997:Time Factors
D000700:Analgesics; D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C073839:SR 48968