Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice

We found that intraperitoneal injection of organic acids, such as propionic and lactic acid, are able to develop writhing responses in mice similarly as that of acetic acid. These acid-induced writhing reactions were signific antly attenuated by capsazepine, a VR1 receptor-specific antagonist, but th e phenylbenzoquinone-induced one was not, suggesting that the acids but not phenylbenzoquinone activate the VRI receptor, which is involved in polymod al pain perception. Hoe 140, a bradykinin B-2 receptor antagonist, also sup pressed the acid-induced writhing response. Furthermore, these writhing res ponses were significantly suppressed after neonatal treatment with capsaici n, which treatment is known to destroy peripheral sensory afferent C-fibers . Capsazepine and Hoe 140 did not further attenuate the already reduced wri thing responses of capsaicin-treated mice, suggesting that the acids stimul ate the VRI and the bradykinin B2 receptor in the pathway comprising sensor y afferent C-fibers. On the other hand, indomethacin further significantly suppressed the writhing number of the capsaicin-treated animals, suggesting that the acid-induced pain perception requires prostanoid receptors not on ly in the pathway via capsaicin-sensitive C-fibers but also in other sensor y pathways. These results provide the first evidence for the involvement of the vanilloid receptor in the acid-induced inflammatory pain perception vi a sensory C-fibers in addition to the known mediators bradykinin, neurokini ns, and prostanoids. (C) 2001 Elsevier Science Inc. All rights reserved.