TRPV1 signals for Inflammatory Pain and Itch

Abstract

TRPV1 is a ligand-gated cation channel activated by capsaicin, acid and heat. Because TRPV1 is activated by pain producing agent, capsaicin, thus, it is presumed to mediate an inflammatory pain. Indeed, some types of thermal pain are reduced in TRPV1-deficient mice. Previously, we showed that metabolic products of lipoxygenase (LO) such as 12-HPETE activate TRPV1. Because metabolites of LO mediate inflammatory processes, activation of capsaicin receptors by metabolites of LO further suggests a role of the receptor in mediating inflammatory pain. Bradykinin, a potent algogenic substance released in response to injury, initiates multiple inflammatory responses and excites sensory neurons. In this symposium, lines of evidence that suggest that bradykinin excite sensory neuron by opening the capsaicin receptor via the PLA2/LO pathway will be discussed. In addition, we also present unequivocal evidence that histamine, another inflammatory mediator, also uses the PLA₂/LO/TRPV1 pathway for excitation of sensory neurons. Application of histamine caused robust scratching behaviors in mice in capsazepine, quinacrine, and NDGA dependent pathways. Furhtermore, the scratching induced by histmamin was much reduced in TRPV1 deficient mice. Because histamine is a major pruritogenic (itch causing) substance, identification of the histamine signaling pathway is much helpful to developing anti-pruritogenic substance to cure itch sensation in atopic dermatitis patients. This finding identifies a mechanism that might be targeted in the development of new therapeutic strategies for the treatment of inflammatory pain or itch. [J Physiol Sci. 2007;57 Suppl:S36]