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. 2020 Oct 21;17:312. doi: 10.1186/s12974-020-01995-y

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — Schematic results of the current study. (1) Hsp70 is expressed in the pulpal tissue following tooth pulp exposure. (2) Hsp70 is axonally transported from the inflamed tooth pulp of the lower first molar to the trigeminal ganglion. (3) Transported Hsp70 is released into the intercellular space in the trigeminal ganglion. (4) Hsp70 binds to the toll-like receptor 4 of trigeminal ganglion neurons innervating the tongue and promotes IL-1RI expression. (5) Simultaneously, the accumulated macrophages following tooth pulp inflammation generate and release IL-1β in the extracellular space in the trigeminal ganglion. Larger amounts of IL-1β bind to the larger number of IL-1RI of trigeminal ganglion neurons innervating the tongue. (6) The IL-1β/IL-1RI signaling facilitates TRPV1 expression. (7) Enhanced expression of TRPV1 on the tongue-innervating trigeminal ganglion neurons promotes neuronal excitability and results in mechanical and heat hypersensitivity of the tongue