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Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation

BACKGROUND: The purpose of the present study is to evaluate the mechanisms underlying tongue-referred pain associated with tooth pulp inflammation. METHOD: Using mechanical and temperature stimulation following dental surgery, we have demonstrated that dental inflammation and hyperalgesia correlates...

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Autores principales: Ohara, Kinuyo, Shimizu, Kohei, Matsuura, Shingo, Ogiso, Bunnai, Omagari, Daisuke, Asano, Masatake, Tsuboi, Yoshiyuki, Shinoda, Masamichi, Iwata, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222866/
https://www.ncbi.nlm.nih.gov/pubmed/24267924
http://dx.doi.org/10.1186/1742-2094-10-139
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author Ohara, Kinuyo
Shimizu, Kohei
Matsuura, Shingo
Ogiso, Bunnai
Omagari, Daisuke
Asano, Masatake
Tsuboi, Yoshiyuki
Shinoda, Masamichi
Iwata, Koichi
author_facet Ohara, Kinuyo
Shimizu, Kohei
Matsuura, Shingo
Ogiso, Bunnai
Omagari, Daisuke
Asano, Masatake
Tsuboi, Yoshiyuki
Shinoda, Masamichi
Iwata, Koichi
author_sort Ohara, Kinuyo
collection PubMed
description BACKGROUND: The purpose of the present study is to evaluate the mechanisms underlying tongue-referred pain associated with tooth pulp inflammation. METHOD: Using mechanical and temperature stimulation following dental surgery, we have demonstrated that dental inflammation and hyperalgesia correlates with increased immunohistochemical staining of neurons for TLR4 and HSP70. RESULTS: Mechanical or heat hyperalgesia significantly enhanced in the ipsilateral tongue at 1 to 9 days after complete Freund’s adjuvant (CFA) application to the left lower molar tooth pulp compared with that of sham-treated or vehicle-applied rats. The number of fluorogold (FG)-labeled TLR4-immunoreactive (IR) cells was significantly larger in CFA-applied rats compared with sham-treated or vehicle-applied rats to the molar tooth. The number of heat shock protein (Hsp) 70-IR neurons in trigeminal ganglion (TG) was significantly increased on day 3 after CFA application compared with sham-treated or vehicle-applied rats to the molar tooth. About 9.2% of TG neurons were labeled with DiI applied to the molar tooth and FG injected into the tongue, and 15.4% of TG neurons were labeled with FG injected into the tongue and Alexa-labeled Hsp70-IR applied to the tooth. Three days after Hsp70 or lipopolysaccharide (LPS) application to the tooth in naive rats, mechanical or heat hyperalgesia was significantly enhanced compared with that of saline-applied rats. Following successive LPS-RS, an antagonist of TLR4, administration to the TG for 3 days, the enhanced mechanical or heat hyperalgesia was significantly reversed compared with that of saline-injected rats. Noxious mechanical responses of TG neurons innervating the tongue were significantly higher in CFA-applied rats compare with sham rats to the tooth. Hsp70 mRNA levels of the tooth pulp and TG were not different between CFA-applied rats and sham rats. CONCLUSIONS: The present findings indicate that Hsp70 transported from the tooth pulp to TG neurons or expressed in TG neurons is released from TG neurons innervating inflamed tooth pulp, and is taken by TG neurons innervating the tongue, suggesting that the Hsp70-TLR4 signaling in TG plays a pivotal role in tongue-referred pain associated with tooth pulp inflammation.
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spelling pubmed-42228662014-11-07 Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation Ohara, Kinuyo Shimizu, Kohei Matsuura, Shingo Ogiso, Bunnai Omagari, Daisuke Asano, Masatake Tsuboi, Yoshiyuki Shinoda, Masamichi Iwata, Koichi J Neuroinflammation Research BACKGROUND: The purpose of the present study is to evaluate the mechanisms underlying tongue-referred pain associated with tooth pulp inflammation. METHOD: Using mechanical and temperature stimulation following dental surgery, we have demonstrated that dental inflammation and hyperalgesia correlates with increased immunohistochemical staining of neurons for TLR4 and HSP70. RESULTS: Mechanical or heat hyperalgesia significantly enhanced in the ipsilateral tongue at 1 to 9 days after complete Freund’s adjuvant (CFA) application to the left lower molar tooth pulp compared with that of sham-treated or vehicle-applied rats. The number of fluorogold (FG)-labeled TLR4-immunoreactive (IR) cells was significantly larger in CFA-applied rats compared with sham-treated or vehicle-applied rats to the molar tooth. The number of heat shock protein (Hsp) 70-IR neurons in trigeminal ganglion (TG) was significantly increased on day 3 after CFA application compared with sham-treated or vehicle-applied rats to the molar tooth. About 9.2% of TG neurons were labeled with DiI applied to the molar tooth and FG injected into the tongue, and 15.4% of TG neurons were labeled with FG injected into the tongue and Alexa-labeled Hsp70-IR applied to the tooth. Three days after Hsp70 or lipopolysaccharide (LPS) application to the tooth in naive rats, mechanical or heat hyperalgesia was significantly enhanced compared with that of saline-applied rats. Following successive LPS-RS, an antagonist of TLR4, administration to the TG for 3 days, the enhanced mechanical or heat hyperalgesia was significantly reversed compared with that of saline-injected rats. Noxious mechanical responses of TG neurons innervating the tongue were significantly higher in CFA-applied rats compare with sham rats to the tooth. Hsp70 mRNA levels of the tooth pulp and TG were not different between CFA-applied rats and sham rats. CONCLUSIONS: The present findings indicate that Hsp70 transported from the tooth pulp to TG neurons or expressed in TG neurons is released from TG neurons innervating inflamed tooth pulp, and is taken by TG neurons innervating the tongue, suggesting that the Hsp70-TLR4 signaling in TG plays a pivotal role in tongue-referred pain associated with tooth pulp inflammation. BioMed Central 2013-11-23 /pmc/articles/PMC4222866/ /pubmed/24267924 http://dx.doi.org/10.1186/1742-2094-10-139 Text en Copyright © 2013 Ohara et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ohara, Kinuyo
Shimizu, Kohei
Matsuura, Shingo
Ogiso, Bunnai
Omagari, Daisuke
Asano, Masatake
Tsuboi, Yoshiyuki
Shinoda, Masamichi
Iwata, Koichi
Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
title Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
title_full Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
title_fullStr Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
title_full_unstemmed Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
title_short Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
title_sort toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222866/
https://www.ncbi.nlm.nih.gov/pubmed/24267924
http://dx.doi.org/10.1186/1742-2094-10-139
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