Itch triggers scratching, a behavioural defence mechanism that aids in the removal of harmful irritants and parasites¹. Chemical itch is triggered by many endogenous and exogenous cues, such as pro-inflammatory histamine, which is released during an allergic reaction¹. Mechanical itch can be triggered by light sensations such as wool fibres or a crawling insect². In contrast to chemical itch pathways, which have been extensively studied, the mechanisms that underlie the transduction of mechanical itch are largely unknown. Here we show that the mechanically activated ion channel PIEZO1 (ref. ³) is selectively expressed by itch-specific sensory neurons and is required for their mechanically activated currents. Loss of PIEZO1 function in peripheral neurons greatly reduces mechanically evoked scratching behaviours and both acute and chronic itch-evoked sensitization. Finally, mice expressing a gain-of-function Piezo1 allele⁴ exhibit enhanced mechanical itch behaviours. Our studies reveal the polymodal nature of itch sensory neurons and identify a role for PIEZO1 in the sensation of itch.

瘙痒会引发抓挠，这是一种有助于去除有害刺激物和寄生虫的行为防御机制¹。化学瘙痒是由许多内源性和外源性线索触发的，例如在过敏反应过程中释放的促炎组胺¹。机械性瘙痒可由羊毛纤维或爬行昆虫²等轻微感觉触发。与已广泛研究的化学瘙痒途径相比，机械瘙痒传导的机制在很大程度上是未知的。在这里，我们展示了机械激活的离子通道 PIEZO1（参考文献³) 由瘙痒特异性感觉神经元选择性表达，并且是其机械激活电流所必需的。外周神经元中 PIEZO1 功能的丧失大大降低了机械诱发的抓挠行为以及急性和慢性瘙痒诱发的致敏性。最后，表达功能获得性Piezo1等位基因⁴的小鼠表现出增强的机械瘙痒行为。我们的研究揭示了瘙痒感觉神经元的多模态性质，并确定了 PIEZO1 在瘙痒感觉中的作用。