Abstract
Bradykinin (BK) produced in damaged and inflamed tissues causes pain and hyperalgesia through the excitation and sensitization of nociceptors. BK shifts down the threshold temperature of a nociceptive heat transducer TRPV1 to below the skin temperature, suggesting that BK-induced pain is a result of TRPV1 activation at the skin temperature. To confirm this hypothesis, we examined the contribution of TRPV1 in BK-induced pain, by comparison of nociceptive responses induced by BK between wild-type (WT) and TRPV1 knockout (KO) mice.
When BK was injected into the plantar skin of the hind paw, incidence of the animals that displayed pain-relating licking behavior and total period of licking were significantly reduced in KO mice compared to wild-type (WT) at a lower dose of BK (0.1nmol), while no difference was observed at the highest dose applied (1nmol). This suggests that TRPV1 is involved in BK-induced pain sensation in vivo, but its contribution is not essential at high dose of BK. Single fiber recording from an isolated skin-saphenous nerve revealed that BK excited nociceptive C-fibers in a dose-dependent manner in KO mice, and no difference was observed in the incidence of BK-sensitive C-fibers and the amplitude of excitation in both mice. In addition, increase of intracellular Ca2+ level by BK was observed in almost same percentage of cultured dorsal root ganglion neurons derived from KO and WT mice. These results suggest partial contribution of TRPV1 to BK-induced pain. [Jpn J Physiol 54 Suppl:S170 (2004)]
