LAUSR

Transient receptor potential vanilloid type-1 (TRPV1) channels have crucial roles in inflammatory hyperalgesia. Different inflammatory mediators can modulate TRPV1 sensitization. Bradykinin is an algogenic substance released at the site of inflammation. The aim of the present study is to investigate the desensitization of TRPV1 receptor by nonpungent agonists and to determine how bradykinin and prostaglandin E2 receptors (EP3 and EP4) modulate the resensitization of TRPV1 receptor after being desensitized by nonpungent agonists. Tail flick test was used to investigate capsaicin-induced thermal hyperalgesia and the desensitization of TRPV1 by the nonpungent agonists (olvanil and arvanil) in male BALB/c mice weighed (22–25 g). Resensitization of TRPV1 by bradykinin and the role of prostaglandin receptors in mediating sensitization of TRPV1 were also investigated. Intraplantar injection of capsaicin (0.3 µg) produced a robust thermal hyperalgesia in mice, while olvanil (0.3 µg) or arvanil (0.3 µg) produced no hyperalgesia, emphasizing their lack of pungency. Olvanil and arvanil significantly attenuated capsaicin-induced thermal hyperalgesia in mice. Bradykinin significantly reversed the desensitizing effects of arvanil, but not olvanil. EP4 but not EP3 receptors mediate the sensitization of TRPV1 By bradykinin in vivo. The present study provides evidence for a novel signaling pathway through which bradykinin can regulate the TRPV1 ion channel function via EP4 receptor.