Intradental mechano-nociceptors serve as sentinels that prevent tooth damage

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<sup>2+</sup> 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<sub>v</sub>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.

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Publication Details

Journal
Cell Reports
Published
2025-07-16
DOI
https://doi.org/10.1016/j.celrep.2025.116017
Citations
5
Primary Topic
Pain Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
5.82

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article

Intradental mechano-nociceptors serve as sentinels that prevent tooth damage

L. Liu, Maximilian Nagel, Joshua J. Emrick, Kevin P. Pipe et al.
5 citations
Cell Reports
Pain Mechanisms and Treatments
5.82
article

Intradental mechano-nociceptors serve as sentinels that prevent tooth damage

L. Liu, Maximilian Nagel, Joshua J. Emrick, Kevin P. Pipe, Elizabeth A. Ronan, Yujia Hu, Mak E. Guenther, Kaitlyn J. Blumberg, Karin H. Uchima Koecklin, Akash Gandhi, Tomer Stern, Bing Ye, Peng Li, Brian S.C. Constantinescu, Aditi Jha, Leen Dakhilalla, Isaac T Berthaume, Shuhao Wan
article en
5 citations

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 Ca<sup>2+</sup> 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<sub>v</sub>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.

Cell ReportsVol. 44(8)
University of Michigan (US), National Center for Complementary and Integrative Health (US)
National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Center for Complementary and Integrative Health
Zero hunger
Openalex Percentile: Top 4%
Pain Mechanisms and Treatments
5.82
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