Bautista Diana M, Jordt Sven-Eric, Nikai Tetsuro, Tsuruda Pamela R, Read Andrew J, Poblete Jeannie, Yamoah Ebenezer N, Basbaum Allan I, Julius David
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell. 2006 Mar 24;124(6):1269-82. doi: 10.1016/j.cell.2006.02.023.
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.
TRPA1是一种兴奋性离子通道，芥末和大蒜中的刺激性物质可作用于该通道。TRPA1被认为在多种感觉过程中发挥作用，包括热（冷）痛觉、听觉和炎性疼痛。通过使用TRPA1基因敲除小鼠，我们现在发现该通道是芥末油和大蒜激活初级传入伤害感受器以产生炎性疼痛的唯一靶点。TRPA1也是环境刺激物（如丙烯醛）的作用靶点，丙烯醛可导致催泪瓦斯、汽车尾气和化疗药物代谢副产物的毒性和炎性作用。TRPA1基因敲除小鼠表现出正常的冷敏感性和未受损的听觉功能，这表明该通道对于有害寒冷或声音的初始检测并非必需。然而，TRPA1基因敲除小鼠在缓激肽诱发的伤害感受器兴奋和疼痛超敏反应方面表现出明显缺陷。因此，TRPA1是转导机制的一个重要组成部分，通过该机制，环境刺激物和内源性促痛剂使伤害感受器去极化，从而引发炎性疼痛。
