2025/07/16 by Elizabeth A. Ronan, Akash Gandhi, Karin H. Uchima Koecklin +15 · 1 voice · 1 citation
Medicine · #Pain Mechanisms and Treatments #Acupuncture Treatment Research Studies #Thermoregulation and physiological responses
paper · pdf · doi:10.1016/j.celrep.2025.116017
openalex publication_date 2025/07/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
The trigeminal sensory neurons that innervate the tooth's vital interior—intradental neurons—are expected to drive severe pain, yet their contribution to healthy tooth sensation has not been explored. Here, we uncover a role for myelinated high-threshold mechano-nociceptors (intradental HTMRs) in tooth protection using in vivo Ca 2+ imaging, opto-/chemogenetics, and the AI-driven behavioral analysis tool LabGym. Intradental HTMRs innervate the inner dentin through overlapping receptive fields and respond as the external structures of the tooth are damaged in the absence of either PIEZO2 or Na v 1.8. Whereas chemogenetic activation of intradental HTMRs results in a pain phenotype marked by facial and postural changes, their transient optogenetic activation triggers a rapid, jaw-opening reflex via contraction of the digastric muscle. Our work indicates that intradental HTMRs not only trigger pain but also protect the teeth by initiating a reflexive movement of the jaws when the teeth experience damage during chewing.