ABSTRACT
TRPA1 is another validated target for pain. It colocalizes with TRPV1 and markers of peptidergic nociceptors.5 The expression of TRPA1 is increased in inŸ ammatory and neuropathic pain models, as well as in avulsion-injured human dorsal root ganglion (DRG) neurons.6 TRPA1 is activated by noxious cold, intracellular Ca2+, hypertonic solutions, and, most prominently, by numerous electrophilic compounds, including active ingredients of pungent natural products (e.g., allyl isothiocyanate or AITC), environmental irritants (acrolein), and endogenous molecules involved in pain, oxidative stress, and inŸammation (e.g., 4-hydroxynonenal or 4-HNE, 15-dPGJ2, H2O2).7,8 TRPA1 knockout mice exhibit de—cits in pain hypersensitivity to agonists and bradykinin; also, treatment with antisense oligodeoxynucleotides and small molecular antagonists attenuate pain in inŸamed and neuropathic rats.9-11 Collectively, these studies support the role of TRPA1 in sensory function and its utility as a pain target.
