recent studies indicate that trpa1 is activated by a number of reactive (allyl isothiocyanate, cinnamaldehyde, farnesyl thiosalicylic acid, formalin, hydrogen peroxide, 4-hydroxynonenal, acrolein, and tear gases) and non-reactive compounds (nicotine, pf-4840154) and considered as a "chemosensor" in the body. trpa1 is co-expressed with trpv1 on nociceptive primary afferent c-fibers in humans. this sub-population of peripheral c-fibers is considered important sensors of nociception in humans and their activation will under normal conditions give rise to pain. indeed, trpa1 is considered as an attractive pain target. trpa1 knockout mice showed near complete attenuation of nocifensive behaviors to formalin, tear-gas and other reactive chemicals . trpa1 antagonists are effective in blocking pain behaviors induced by inflammation (complete freund's adjuvant and formalin).