Understanding the mechanism of peripheral pain sensation has progressed remarkably in recent years, in part thanks to the discovery of transient receptor potential (TRP) ion channels in sensory neurons. Among these ion channels, the TRPA1 subtype is attracting attention because of its ability to sense a wide spectrum of damage signals from external and internal environments, which provides for a novel paradigm for the modulation of ion channels. In this Perspective, we focus on the TRPA1 ligands and cofactors, which are grouped in terms of their reactivity and binding fashions. The mechanism(s) of binding and possible pharmacological implications on TRPA1 will also be discussed because the polymodality of TRPA1 in signal sensing suggests that this channel may be a promising target for pain modulation.
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