Emerging roles of TRPA1 in sensation of oxidative stress and its implications in defense and danger

Transient receptor potential ankyrin subtype 1 (TRPA1) is a well-known ion channel that play a central role for pain sensation. In the peripheral sensory nerve terminals innervating the body tegument or organs, TRPA1 detects and is activated by diverse harmful environmental and internal stimuli. The TRPA1 activation results in neuronal firing, which finally sends a warning signal to our brain. However, sensitization or sustained activation of TRPA1 often causes plastic changes both in the neural pathway and in the peripheral tissues, leading to a pathologic state in tissue health and pain mediation. Recently, a unique covalent detection mode for reactive biological attacks was uncovered in the sensory mechanisms of TRPA1. Notably, the pool of the newly found reactive stimulators for TRPA1 includes oxidative stress. Here, we overview the nature of this interaction, and try to find biological meanings of the participation of such a rapid ionotrophic component in disease exacerbations. Acutely, its relatively rapid response can be understood in terms of efficiency for avoiding harmful milieu as quickly as possible, as implicated in the raison d'etre of the pain mechanism. Nonetheless, complex situations in a chronic disease progress may occur. As well, multiple interplays with known molecules on the redox defense mechanism are anticipated. At a therapeutic angle, how to control TRPA1 for promoting body's defensive potential will be a practical question but remains to be answered. Future investigations will likely give more detailed insights to understand the roles and target validity of TRPA1.