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Porphyromonas gingivalis lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain
Author(s) -
Kaewpitak A.,
Bauer C. S.,
Seward E. P.,
Boissonade F. M.,
Douglas C. W. I.
Publication year - 2020
Publication title -
international endodontic journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.988
H-Index - 119
eISSN - 1365-2591
pISSN - 0143-2885
DOI - 10.1111/iej.13282
Subject(s) - porphyromonas gingivalis , lipopolysaccharide , medicine , sensory system , neuroscience , trigeminal ganglion , dentistry , psychology , periodontitis
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 −1 ) on calcium signalling was assessed (by calcium imaging using Cal‐520 AM) in comparison with the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100 μmol L −1 ), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1 μmol L −1 ) and high potassium (60 mmol L −1 KCl). TG cultures were pre‐treated with either 1 μmol L −1 CLI‐095 to block Toll‐like receptor 4 (TLR4) signalling or with 3 μmol L −1 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 Porphyromonas 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 Porphyromonas gingivalis LPS directly activated 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.