The initiation of somatic touch sensation begins with direct pressure stimulation of mechanically activated (MA) channels located in the nerve endings of dorsal root ganglion (DRG) neurons. PIEZO1 has been identified as a rapidly adapting MA channel, yet its involvement in mechanical pain remains unknown. Here, we employed fluorescence in situ hybridization, calcium imaging, whole-cell patch-clamp recordings, and behavioral assays in mice to elucidate the pivotal role of PIEZO1 in mechanical pain transmission. Our findings reveal the expression of PIEZO1 in a subset of DRG neurons associated with nociceptors expressing TRPV1 rather than MRGPRD. To further comprehend the physiological roles of PIEZO1 in DRG neurons, we classified them based on the type of MA currents; notably, silencing PIEZO1 using short hairpin RNA (shRNA) virus significantly attenuated intermediately adapting and intermediately slowly adapting responses. Moreover, we observed a decrease in formalin- and carrageenan-induced nocifensive behaviors following ganglionic injection of PIEZO1 shRNA virus in mice. Together, our results suggest that PIEZO1 serves as a nociceptive MA channel, mediating mechanical pain in the context of inflammation.