Ronan Elizabeth A, Gandhi Akash R, Constantinescu Brian S C, Uchima Koecklin Karin H, Guenther Mak E, Nagel Maximilian, Blumberg Kaitlyn J, Stern Tomer, Li Peng, Emrick Joshua J
bioRxiv. 2024 May 12:2024.05.11.593684. doi: 10.1101/2024.05.11.593684.
Pain is the anticipated output of the trigeminal sensory neurons that innervate the tooth's vital interior ; however, the contribution of intradental neurons to healthy tooth sensation has yet to be defined. Here, we employ in vivo Ca imaging to identify and define a population of myelinated high-threshold mechanoreceptors (intradental HTMRs) that detect superficial structural damage of the tooth and initiate jaw opening to protect teeth from damage. Intradental HTMRs remain inactive when direct forces are applied to the intact tooth but become responsive to forces when the structural integrity of the tooth is compromised, and the dentin or pulp is exposed. Their terminals collectively innervate the inner dentin through overlapping receptive fields, allowing them to monitor the superficial structures of the tooth. Indeed, intradental HTMRs detect superficial enamel damage and encode its degree, and their responses persist in the absence of either PIEZO2 or Na 1.8 . Optogenetic activation of intradental HTMRs triggers a rapid, jaw opening reflex via contraction of the digastric muscle. Taken together, our data indicate that intradental HTMRs serve as sentinels that guard against mechanical threats to the tooth, and their activation results in physical tooth separation to minimize irreversible structural damage. Our work provides a new perspective on the role of intradental neurons as protective rather than exclusively pain-inducing and illustrates additional diversity in the functions of interoreceptors.
疼痛是支配牙齿重要内部结构的三叉神经感觉神经元预期的输出结果;然而,牙内神经元对健康牙齿感觉的贡献尚未明确。在此,我们采用体内钙成像技术来识别和定义一群有髓鞘的高阈值机械感受器(牙内高阈值机械感受器),它们能检测牙齿的表面结构损伤并引发张口动作以保护牙齿免受损伤。当对完整牙齿施加直接力时,牙内高阈值机械感受器保持不活跃状态,但当牙齿的结构完整性受到破坏且牙本质或牙髓暴露时,它们会对力产生反应。它们的终末通过重叠的感受野共同支配牙本质内层,使它们能够监测牙齿的表面结构。事实上,牙内高阈值机械感受器能检测到牙釉质表面损伤并对其程度进行编码,并且在缺乏PIEZO2或Na 1.8的情况下它们的反应依然存在。牙内高阈值机械感受器的光遗传学激活通过二腹肌收缩触发快速的张口反射。综上所述,我们的数据表明牙内高阈值机械感受器充当着防范牙齿机械性威胁的哨兵,它们的激活会导致牙齿物理分离,以将不可逆的结构损伤降至最低。我们的工作为牙内神经元的作用提供了一个新视角,即其具有保护作用而非仅仅诱发疼痛,并说明了内感受器功能的额外多样性。