Mechanically Activated Piezo Channels Mediate Touch and Suppress Acute Mechanical Pain Response in Mice

Abstract

Summary: Touch and mechanical pain represent distinct, but interactive, modalities of mechanosensation. However, the molecular mechanisms underlying these mechanotransduction processes remain incompletely understood. Here, we show that deletion of the mechanically activated and rapidly adapting Piezo2 channel in a portion of the low-threshold mechanoreceptors and a majority of the IB4-positive nociceptors impairs touch but sensitizes mechanical pain in mice. Ectopic expression of the Piezo2 homolog, the intermediately adapting Piezo1 channel, in sensory neurons can sensitize touch in normal mice and rescue defective touch of the Piezo2-knockout mice. Broad expression of Piezo1 in sensory neurons decreases, rather than evokes, mechanical pain responses. Together, our data suggest that Piezo channels can mediate touch and indirectly suppress acute pain. Tuning Piezo-mediated touch sensitivity allows us to recapitulate the inhibitory effect of touch on acute pain in mouse models. : Using conditional deletion of endogenously expressed Piezo2 or ectopic expression of Piezo1 in primary somatosensory neurons, Zhang et al. find that mechanically activated Piezo channels can mediate touch and proprioception as well as indirectly suppress acute mechanical pain responses in mice. Keywords: Piezo1, Piezo2, mechanosensitive ion channels, DRG, mechanosensation, touch, pain, proprioception