Piezo1 mediates mechanical signals in TRPV1‐positive nociceptors in mice

Abstract Aim This investigation addresses Piezo1's expression and mechanistic role in dorsal root ganglion (DRG) neurons and delineates its participation in mechanical and inflammatory pain modulation. Methods We analyzed Piezo1's expression patterns in DRG neurons and utilized Piezo1‐specific shRNA to modulate its activity. Electrophysiological assessments of mechanically activated (MA) currents in DRG neurons and behavioral analyses in mouse models of inflammatory pain were conducted to elucidate Piezo1's functional implications. Additionally, we investigated the excitability of TRPV1‐expressing DRG neurons, particularly under inflammatory conditions. Results Piezo1 was preferentially expressed in DRG neurons co‐expressing the TRPV1 nociceptor marker. Knockdown of Piezo1 attenuated intermediately adapting MA currents and lessened tactile pain hypersensitivity in models of inflammatory pain. Additionally, silencing Piezo1 modified the excitability of TRPV1‐expressing neurons under inflammatory stress. Conclusion Piezo1 emerges as a key mediator in the transmission of mechanical and inflammatory pain, indicating its potential as a novel target for pain management therapies. Our finding not only advances the understanding of nociceptive signaling but also emphasizes the therapeutic potential of modulating Piezo1 in the treatment of pain.