The ion channel TRPA1 is required for chronic itch.
The ion channel TRPA1 is required for chronic itch.
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DOI：
10.1523/jneurosci.5318-12.2013
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发表时间：
2013-05-29
期刊：
影响因子：
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通讯作者：
Bautista DM
中科院分区：
文献类型：
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作者：
Wilson SR;Nelson AM;Batia L;Morita T;Estandian D;Owens DM;Lumpkin EA;Bautista DM
慢性瘙痒是一种使人衰弱的疾病，影响十分之一的人。对初级感觉神经元和皮肤中介导慢性瘙痒的分子知之甚少。我们证明了离子通道TRPA1是慢性瘙痒所必需的。使用慢性瘙痒的小鼠模型，我们表明，由受损的皮肤屏障引起的抓挠在TRPA1缺陷动物中被消除。该模型概括了在流行的人类疾病如特应性皮炎和银屑病中观察到的慢性瘙痒的许多病理生理学特征，包括强烈的抓挠、广泛的表皮增生以及感觉神经元和皮肤中基因表达的显著变化。值得注意的是，TRPA1是将慢性瘙痒信号转导到CNS和由干燥皮肤诱发的瘙痒和抓挠引发的剧烈皮肤变化所必需的。这些数据表明，TRPA1调节瘙痒转导和皮肤中促进慢性瘙痒的病理生理变化。
Chronic itch is a debilitating condition that affects one in 10 people. Little is known about the molecules that mediate chronic itch in primary sensory neurons and skin. We demonstrate that the ion channel TRPA1 is required for chronic itch. Using a mouse model of chronic itch, we show that scratching evoked by impaired skin barrier is abolished in TRPA1-deficient animals. This model recapitulates many of the pathophysiological hallmarks of chronic itch that are observed in prevalent human diseases such as atopic dermatitis and psoriasis, including robust scratching, extensive epidermal hyperplasia, and dramatic changes in gene expression in sensory neurons and skin. Remarkably, TRPA1 is required for both transduction of chronic itch signals to the CNS and for the dramatic skin changes triggered by dry-skin-evoked itch and scratching. These data suggest that TRPA1 regulates both itch transduction and pathophysiological changes in the skin that promote chronic itch.