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Abstract
TRPA1 is an excitatory ion channel targeted by pungent irritants from mustard and
garlic. TRPA1 has been proposed to function in diverse sensory processes, including
thermal (cold) nociception, hearing, and inflammatory pain. Using TRPA1-deficient
mice, we now show that this channel is the sole target through which mustard oil and
garlic activate primary afferent nociceptors to produce inflammatory pain. TRPA1 is
also targeted by environmental irritants, such as acrolein, that account for toxic
and inflammatory actions of tear gas, vehicle exhaust, and metabolic byproducts of
chemotherapeutic agents. TRPA1-deficient mice display normal cold sensitivity and
unimpaired auditory function, suggesting that this channel is not required for the
initial detection of noxious cold or sound. However, TRPA1-deficient mice exhibit
pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity.
Thus, TRPA1 is an important component of the transduction machinery through which
environmental irritants and endogenous proalgesic agents depolarize nociceptors to
elicit inflammatory pain.