Fig. 4: OS of Piezo2⁺ mechanical nociception promotes CGRP release.

a–d Schematic diagram of Piezo2::ChR2 transgenic mouse construction and Piezo2 immunofluorescence staining in DRG, sciatic nerve, and tibial upper bone tissue, scale bar: 100 μm. (4a Created in BioRender. m*[POEj,m*. (2025) https://BioRender.com/h48v716). e, f Diagram of the OS device implanted around the DRG and the release of neuropeptides in the target area caused by OS of DRG in mice expressing ChR2. g Changes in mechanical sensitivity in Piezo2::ChR2 mice under OS. Data are presented as mean ± SEM (n  =  5 biologically independent experiments). P-values were calculated using one-way ANOVA with Tukey’s multiple comparisons test. h Changes in heat sensitivity in Piezo2::ChR2 mice under OS. Data are presented as mean ± SEM (n  =  5 biologically independent experiments). P-values were calculated using one-way ANOVA with Tukey’s multiple comparisons test. i Changes in aversive behavior in Piezo2-Cre⁺ and Piezo2-Cre⁻ mice under OS. Data are presented as mean ± SEM (n  =  5 biologically independent experiments). P-values were calculated using Two-tailed Student’s t tests. j–m ELISA experiment of neuropeptide release in the DRG target area of Piezo2::ChR2 mice under OS. Data are presented as mean ± SEM (n  =  5 biologically independent experiments). P-values were calculated using one-way ANOVA with Tukey’s multiple comparisons test. (ChR2: channelrhodopsin-2, CGRP: calcitonin gene-related peptide, SP: Substance P, NPY: neuropeptide Y, VIP: vasoactive intestinal peptide). Source data are provided as a Source Data file.