Intradental mechano-nociceptors serve as sentinels that prevent tooth damage

牙内机械伤害感受器如同哨兵一般,能够防止牙齿损伤。

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作者:Elizabeth A Ronan ,Akash R Gandhi ,Karin H Uchima Koecklin ,Yujia Hu ,Shuhao Wan ,Brian S C Constantinescu ,Mak E Guenther ,Maximilian Nagel ,Ling-Yu Liu ,Aditi Jha ,Leen Dakhilalla ,Kaitlyn J Blumberg ,Isaac T Berthaume ,Tomer Stern ,Kevin P Pipe ,Bing Ye ,Peng Li ,Joshua J Emrick

Abstract

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 Ca2+ 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 Nav1.8. 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.

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