Piezo1 transduces inflammatory pain signals in nociceptors

Abstract Mechanosensation begins with sensing pressure by mechanically activated (MA) channels in the nerve endings of dorsal root ganglion (DRG) neurons. Piezos are the first discovered MA channels in mammals with various mechanosensations. Piezo2’s function is mainly linked to light touch, nociception, and proprioception in DRGs. However, the involvement of Piezo1 in mechanical pain has remained uncertain. Here, we report that Piezo1 transcripts are distinctively expressed in DRGs whose population is largely positive for Trpv1. Similarly, Yoda1, a Piezo1 agonist, induces robust Ca2+ elevation among capsaicin-positive populations. DRG neurons infected with Piezo1 shRNA virus result in a reduction of intermediately-adapting type of MA currents. Silencing Piezo1 reduces tactile pain hypersensitivity in formalin- and carrageenan-dependent inflammation. Furthermore, Piezo1 ablation in DRGs induces excitability change within capsaicin-positive populations. Our findings suggest that Piezo1 is an MA channel mediating mechanical pain in DRGs.