TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents

Diana M. Bautista, Sven Eric Jordt, Tetsuro Nikai, Pamela R. Tsuruda, Andrew J. Read, Jeannie Poblete, Ebenezer N. Yamoah, Allan I. Basbaum, David Julius

Research output: Contribution to journalArticle

1297 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1269-1282
Number of pages14
JournalCell
Volume124
Issue number6
DOIs
StatePublished - Mar 24 2006

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Bautista, D. M., Jordt, S. E., Nikai, T., Tsuruda, P. R., Read, A. J., Poblete, J., Yamoah, E. N., Basbaum, A. I., & Julius, D. (2006). TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents. Cell, 124(6), 1269-1282. https://doi.org/10.1016/j.cell.2006.02.023