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 imp rove the treatment of patients with such syndrome. The aim of the present w ork was to elucidate the possible involvement of spinal substance P and neu rokinin A in the mechanical and thermal allodynia observed in streptozocin- induced diabetic rats. A tachykinin NK, receptor antagonist, RP-67,580 ((3a R,7aR)-7,7-diphenyl-2(1-imino-2(2-methoxy phenyl)-ethyl) perhydroisoindol-4 -one hydrochloride), a tachykinin NK, receptor antagonist, SR-48,968 ((S)-N -methyl (4-(acetylamino-4phenylpiperidino)-2-(3,4-dichlorophenyl) butyl) be nzamide) and their respective enantiomers were intrathecally administered 4 weeks after the induction of diabetes. Mechanical and thermal allodynia we re evaluated before and up to 60 min after injection. The tachykinin recept or antagonists at the highest doses (10 and 25 mu g) significantly reduced allodynia, their enantiomers being inactive. Both of these data suggest the involvement of substance P and neurokinin A in the neuropathy-induced allo dynia and offer a novel hypothesis to treat chronic pain due to diabetes. ( C) 2000 Elsevier Science B.V. All rights reserved.