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  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2021; 30(5): 329-340

Published online October 31, 2021

https://doi.org/10.5607/en21018

© The Korean Society for Brain and Neural Sciences

Upregulation of Toll-like Receptor 2 in Dental Primary Afferents Following Pulp Injury

Pa Reum Lee, Jin-Hee Lee, Ji Min Park and Seog Bae Oh*

Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-740-8656, FAX: 82-2-762-5107
e-mail: odolbae@snu.ac.kr
These authors contributed equally to this work.

Received: June 19, 2021; Revised: October 23, 2021; Accepted: October 24, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Pulpitis (toothache) is a painful inflammation of the dental pulp and is a prevalent problem throughout the world. This pulpal inflammation occurs in the cells inside the dental pulp, which have host defense mechanisms to combat oral microorganisms invading the pulp space of exposed teeth. This innate immunity has been well studied, with a focus on Toll-like receptors (TLRs). The function of TLR4, activated by Gram-negative bacteria, has been demonstrated in trigeminal ganglion (TG) neurons for dental pain. Although Gram-positive bacteria predominate in the teeth of patients with caries and pulpitis, the role of TLR2, which is activated by Gram-positive bacteria, is poorly understood in dental primary afferent (DPA) neurons that densely innervate the dental pulp. Using Fura-2 based Ca2+ imaging, we observed reproducible intracellular Ca2+ responses induced by Pam3CSK4 and Pam2CSK4 (TLR2-specific agonists) in TG neurons of adult wild-type (WT) mice. The response was completely abolished in TLR2 knock-out (KO) mice. Single-cell RT-PCR detected Tlr2 mRNA in DPA neurons labeled with fluorescent retrograde tracers from the upper molars. Using the mouse pulpitis model, real-time RT-PCR revealed that Tlr2 and inflammatory-related molecules were upregulated in injured TG, compared to non-injured TG, from WT mice, but not from TLR2 KO mice. TLR2 protein expression was also upregulated in injured DPA neurons, and the change was corresponded with a significant increase in calcitonin gene-related peptide (CGRP) expression. Our results provide a better molecular understanding of pulpitis by revealing the potential contribution of TLR2 to pulpal inflammatory pain.

Graphical Abstract


Keywords: Neurobiology, Dental pulp exposure, Pulpitis, Toll-like receptors, Trigeminal nerve