Involvement of peripheral TRPV1 in intramuscular-acid–induced mechanical hyperalgesia. The withdrawal responses of mouse hind paws to a 0.2-mN bending force in Trpv1+/+ and Trpv1−/− mice before and after intramuscular acid injection. (A) Trpv1+/+ and (B) Trpv1−/− mice were injected with pH 4.0 saline on days 0 and 5. (C) Co-injection of acid with capsazepine (1 nmole) at the first injection did not affect the development of hyperalgesia to the repeated acid injection in wild-type (WT) mice. (D) Capsazepine (1 nmole) at the second acid injection did not affect the development of hyperalgesia. (E) Capsazepine (1 nmole) at both acid injections prevented the development of long-lasting hyperalgesia. (F) Dual acid injections induced long-lasting hyperalgesia more than 19 days. (G) Coinjection of acid with capsazepine (1 nmole) at day 0 resulted in short-lasting hyperalgesia, for 7 days. Black arrows indicate when mice received the intramuscular acid injection. Red arrows indicate when mice received the co-injection of acid with capsazepine. B, baseline on day 0; D, day. *P < 0.05 compared with the response before the second acid injection.