TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.
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.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Diana M
DM
Bautista
Sven-Eric
SE
Jordt
Tetsuro
T
Nikai
Pamela R
PR
Tsuruda
Andrew J
AJ
Read
Jeannie
J
Poblete
Ebenezer N
EN
Yamoah
Allan I
AI
Basbaum
David
D
Julius
D000171:Acrolein / Q000633:toxicity; D000818:Animals; D003080:Cold Temperature; D016057:Evoked Potentials, Auditory, Brain Stem; D005737:Garlic; D007249:Inflammation / Q000276:immunology; D019570:Inhalation Exposure; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D009619:Nociceptors / Q000187:drug effects / Q000276:immunology*; D010146:Pain; D000074025:TRPA1 Cation Channel; D013823:Thermoreceptors / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism
D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000171:Acrolein