Piezoelectric actuator-evoked mechano-gated currents in trigeminal neurons innervating the mouse temporomandibular joint

The most burdensome symptom of temporomandibular joint disorders (TMJDs) is mechanically evoked pain. To identify the trigeminal ganglion (TG) neuronal subtypes mediating mechanical sensitivity, we combined whole-cell patch-clamp electrophysiology with immunohistochemistry (IHC) to characterize mouse TMJ-innervating TG neurons retrogradely labeled from the TMJ. Electrophysiological analysis identified five distinct neuronal groups, only one of which responded to piezo actuator-induced mechanical stimulation. TMJ innervation was dominated by C- and A-nociceptors, comprising four of the five identified groups. The fifth, a minor population of small-diameter neurons (S1), displayed properties consistent with either vGlut3-positive, C-low-threshold mechanoreceptors (C-LTMRs) or Sst-positive neurons. Two mechanically insensitive C-nociceptor groups, distinguished by their action potential firing patterns, likely corresponded to CGRP-positive and non-Mrgpr neuronal populations. One mechanically insensitive A-nociceptor group likely represented Smr2-positive Aδ high-threshold mechanoreceptors (Aδ-HTMRs). The only mechanically responsive neurons were large-diameter A-nociceptors, which likely correspond to the weakly TrkC- expressing neuronal population. No recorded neurons displayed electrophysiological characteristics of classical A-LTMRs. Together, these findings demonstrate that the TMJ is innervated by a distinct repertoire of TG sensory neurons compared with the skin and masseter muscle, with mechanically responsive afferents restricted to a single A-nociceptor subtype rather than classical low-threshold mechanoreceptors.