Cooling Relief of Acute and Chronic Itch Requires TRPM8 Channels and Neurons.
Cooling Relief of Acute and Chronic Itch Requires TRPM8 Channels and Neurons.
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DOI：
10.1016/j.jid.2017.12.025
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
McKemy DD
中科院分区：
文献类型：
--
作者：
Palkar R;Ongun S;Catich E;Li N;Borad N;Sarkisian A;McKemy DD
几个世纪以来，冷却或将薄荷油搽剂应用于皮肤已被用于治疗瘙痒，但对诸如这些的反刺激如何诱导瘙痒缓解知之甚少。事实上，在科学文献中没有明确的共识，即冷却是否真的阻止了瘙痒信号的传导，或者它只是一种安慰剂效应。我们理解的这一差距使我们假设，冷却是抗过敏的，并且像冷却镇痛一样，需要冷门控离子通道TRPM 8的功能，TRPM 8是外周传入神经末梢上表达的薄荷醇受体。结合药理学、遗传学和小鼠行为学检测，我们发现冷却抑制组胺能和非组胺能瘙痒通路，并且通过冷却抑制瘙痒需要TRPM8通道或完整和功能性TRPM8表达传入神经元。冷模拟薄荷醇还以TRPM8依赖性方式有效改善瘙痒。此外，我们发现慢性瘙痒可以通过冷却来改善，这表明这种反刺激激活了一种特定的神经回路，从而导致广泛的瘙痒缓解和治疗慢性瘙痒的潜在细胞机制。
Cooling or the application of mentholated liniments to the skin has been used to treat itch for centuries, yet remarkably little is known about how counter-stimuli such as these induce itch relief. Indeed, there is no clear consensus in the scientific literature as to whether or not cooling does in fact block the transduction of itch signals or if it is simply a placebo effect. This gap in our understanding led us to hypothesize that cooling is antipruritic and, like cooling analgesia, requires function of the cold-gated ion channel TRPM8, a receptor for menthol expressed on peripheral afferent nerve endings. Using a combination of pharmacologic, genetic, and mouse behavioral assays, we find that cooling inhibits both histaminergic and non-histaminergic itch pathways, and that inhibition of itch by cooling requires TRPM8 channels or intact and functional TRPM8-expressing afferent neurons. The cold mimetic menthol is also effective in ameliorating itch in a TRPM8-dependent manner. Moreover, we find that chronic itch can be ameliorated by cooling, demonstrating that this counter-stimulus activates a specific neural circuit that leads to broad itch relief and a potential cellular mechanism for treatment of chronic itch.
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DOI：
10.1152/physiol.00007.2011
发表时间：
2011-08
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Jeffry J;Kim S;Chen ZF
通讯作者：
Chen ZF
影响因子：
7.4
作者：
Liu B;Fan L;Balakrishna S;Sui A;Morris JB;Jordt SE
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Jordt SE
影响因子：
4.5
作者：
Liu, Tong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
7.4
作者：
Kichko, TI;Reeh, PW
通讯作者：
Reeh, PW
影响因子：
6.5
作者：
MELTON, FM;SHELLEY, WB
通讯作者：
SHELLEY, WB