title: Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice.
abstract: 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 significantly attenuated by capsazepine, a VR1 receptor-specific antagonist, but the phenylbenzoquinone-induced one was not, suggesting that the acids but not phenylbenzoquinone activate the VR1 receptor, which is involved in polymodal pain perception. Hoe 140, a bradykinin B2 receptor antagonist, also suppressed the acid-induced writhing response. Furthermore, these writhing responses were significantly suppressed after neonatal treatment with capsaicin, which treatment is known to destroy peripheral sensory afferent C-fibers. Capsazepine and Hoe 140 did not further attenuate the already reduced writhing responses of capsaicin-treated mice, suggesting that the acids stimulate the VR1 and the bradykinin B2 receptor in the pathway comprising sensory 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 only in the pathway via capsaicin-sensitive C-fibers but also in other sensory pathways. These results provide the first evidence for the involvement of the vanilloid receptor in the acid-induced inflammatory pain perception via sensory C-fibers in addition to the known mediators bradykinin, neurokinins, and prostanoids.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: A
authors.initials: A
authors.lastname: Ueno
authors.forename: H
authors.initials: H
authors.lastname: Naraba
authors.forename: S
authors.initials: S
authors.lastname: Oh-ishi
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D011422:Propionates / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D011422:Propionates; D011453:Prostaglandins; D011955:Receptors, Drug; D011982:Receptors, Prostaglandin; D019344:Lactic Acid; C029322:phenylbenzoquinone; C065679:icatibant; C029658:propionic acid; C071423:capsazepine; D019342:Acetic Acid; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin