Kaewpitak, A., Bauer, C.S., Seward, E.P. orcid.org/0000-0001-5311-1343 et al. (2 more authors) (2020) Porphyromonas gingivalis lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain. International Endodontic Journal, 53 (6). pp. 846-858. ISSN 0143-2885
Abstract
Aim
To determine whether Porphyromonas gingivalis lipopolysaccharide (LPS) can directly activate trigeminal neurons, to identify which receptors are involved, and to establish whether activation leads to secretion of the neuropeptide calcitonin‐gene related peptide (CGRP) and/or the translocation of NF‐κB.
Methodology
Mouse trigeminal ganglion (TG) cells were cultured in vitro for 2 days. The effect of P. gingivalis LPS (20 μg/mL) on calcium signalling was assessed (by calcium imaging using Cal‐520 AM) in comparison to the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100 μM), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1 μM), and high potassium (60 mM KCl). TG cultures were pre‐treated with either 1 μM CLI‐095 to block Toll‐like receptor 4 (TLR4) signalling or with 3 μM HC‐030031 to block TRPA1 signalling. CGRP release was determined using ELISA, and nuclear translocation of NF‐κB was investigated using immunocytochemistry. Data were analysed by one‐way analysis of variance, followed by Bonferroni’s post‐hoc test as appropriate.
Results
P. gingivalis LPS directly exerted a rapid excitatory response on sensory neurons and non‐neuronal cells (p<0.001 to p<0.05). The effects on neurons appear to be mediated via TLR4‐ and TRPA1‐dependent pathways. The responses were accompanied by an increased release of CGRP (p<0.001) and by NF‐κB nuclear translocation (p<0.01).
Conclusions
P. gingivalis LPS directly activates trigeminal sensory neurons (via TLR4 and TRPA1 receptors) and non‐neuronal cells, resulting in CGRP release and NF‐κB nuclear translocation. This indicates that P. gingivalis can directly influence activity in trigeminal sensory neurons and this may contribute to acute and chronic inflammatory pain.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | mouse; pain; symptomatic pulpitis; TLR4; trigeminal; TRPA1 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Feb 2020 10:33 |
Last Modified: | 10 Dec 2021 10:29 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/iej.13282 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:157154 |