Ronan Elizabeth A, Gandhi Akash R, Uchima Koecklin Karin H, Hu Yujia, Wan Shuhao, Constantinescu Brian S C, Guenther Mak E, Nagel Maximilian, Liu Ling-Yu, Jha Aditi, Dakhilalla Leen, Blumberg Kaitlyn J, Berthaume Isaac T, Stern Tomer, Pipe Kevin P, Ye Bing, Li Peng, Emrick Joshua J
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Rep. 2025 Aug 26;44(8):116017. doi: 10.1016/j.celrep.2025.116017. Epub 2025 Jul 16.
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 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 Na1.8. 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.
支配牙齿重要内部结构(牙髓内神经元)的三叉神经感觉神经元预计会引发剧痛,但其对健康牙齿感觉的贡献尚未得到探索。在这里,我们利用体内钙成像、光遗传学/化学遗传学以及人工智能驱动的行为分析工具LabGym,揭示了有髓鞘高阈值机械性伤害感受器(牙髓内HTMRs)在牙齿保护中的作用。牙髓内HTMRs通过重叠的感受野支配内牙本质,并且在缺乏PIEZO2或Na1.8的情况下,当牙齿外部结构受损时做出反应。虽然牙髓内HTMRs的化学遗传学激活会导致以面部和姿势变化为特征的疼痛表型,但其短暂的光遗传学激活会通过二腹肌收缩触发快速的张口反射。我们的研究表明,牙髓内HTMRs不仅会引发疼痛,还会在牙齿在咀嚼过程中受到损伤时通过引发颌骨的反射性运动来保护牙齿。