PIEZO1 transduces mechanical itch in mice

Rose Z Hill ¹, Meaghan C Loud ¹, Adrienne E Dubin ², Brooke Peet ¹, Ardem Patapoutian ³

¹Howard Hughes Medical Institute, Department of Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.

²Department of Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA.

³Howard Hughes Medical Institute, Department of Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA. ardem@scripps.edu.

Abstract

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.

https://www.nature.com/articles/s41586-022-04860-5#additional-information

Presenter: Hyein Kim