Skeletal muscle-innervating small dorsal root ganglion neurons exhibit greater mechanosensitivity and responsiveness to yoda-1 in rats

Mechanosensitive channels are activated by mechanical stimuli generated during skeletal muscle contraction. These signals are conveyed to the spinal cord via dorsal root ganglion (DRG) neurons. Piezo2 channels are well-recognized mechanoreceptors expressed in DRG neurons innervating skeletal muscle. In contrast, Piezo1 channels have received far less attention in the context of sensory transduction, largely because their expression levels are relatively low, particularly in DRG neurons. As such, the functional role of Piezo1 channels in skeletal muscle-innervating DRG neurons remains incompletely understood. We therefore determined whether skeletal muscle-innervating DRG neurons exhibit Piezo1-like immunoreactivity and functional responsiveness to the Piezo1 agonist Yoda-1, and whether these neurons display distinct mechanosensitivity. We hypothesized that DRG neurons innervating skeletal muscle would exhibit Piezo1-like immunoreactivity and greater mechanosensitivity and responsiveness to Yoda-1 than unlabeled DRG neurons. Skeletal muscle afferent DRG neurons were identified by injection of a fluorescent retrograde tracer (DiI) into rat hindlimb muscle. Immunofluorescence staining revealed that 24±11% of Piezo1-positive small DRG neurons colocalized with DiI. In vitro whole-cell patch clamp recordings demonstrated a significantly lower mechanical threshold in DiI-positive neurons than in DiI-negative neurons ( P = 0.023). Likewise, Yoda-1 evoked significantly greater total charge transfer in DiI-positive than DiI-negative neurons ( P = 0.014). Importantly, DiI positivity was significantly associated with Yoda-1 responsiveness (odds ratio, 3.72; 95% CI, 1.38–10.05, P = 0.010). Collectively, our results demonstrate that skeletal muscle-innervating DRG neurons exhibit greater mechanosensitivity and responsiveness to Yoda-1, supporting functional Piezo1-related signaling in this sensory neuronal population.