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The effect of <jats:italic>P.\u00a0gingivalis<\/jats:italic> LPS (20\u00a0\u03bcg\u00a0mL<jats:sup>\u22121<\/jats:sup>) on calcium signalling was assessed (by calcium imaging using Cal\u2010520 AM) in comparison with the transient receptor potential channel A1 (TRPA1) agonist cinnamaldehyde (CA; 100\u00a0\u03bcmol\u00a0L<jats:sup>\u22121<\/jats:sup>), the TRP channel V1 (TRPV1) agonist capsaicin (CAP; 1\u00a0\u03bcmol\u00a0L<jats:sup>\u22121<\/jats:sup>) and high potassium (60\u00a0mmol\u00a0L<jats:sup>\u22121<\/jats:sup> KCl). TG cultures were pre\u2010treated with either 1\u00a0\u03bcmol\u00a0L<jats:sup>\u22121<\/jats:sup> CLI\u2010095 to block Toll\u2010like receptor 4 (TLR4) signalling or with 3\u00a0\u03bcmol\u00a0L<jats:sup>\u22121<\/jats:sup> HC\u2010030031 to block TRPA1 signalling. CGRP release was determined using ELISA, and nuclear translocation of NF\u2010\u03baB was investigated using immunocytochemistry. Data were analysed by one\u2010way analysis of variance, followed by Bonferroni\u2019s <jats:italic>post hoc<\/jats:italic> test as appropriate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS directly exerted a rapid excitatory response on sensory neurons and non\u2010neuronal cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 to <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). The effects on neurons appear to be mediated via TLR4\u2010 and TRPA1\u2010dependent pathways. The responses were accompanied by an increased release of CGRP (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and by NF\u2010\u03baB nuclear translocation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS directly activated trigeminal sensory neurons (via TLR4 and TRPA1 receptors) and non\u2010neuronal cells, resulting in CGRP release and NF\u2010\u03baB nuclear translocation. This indicates that <jats:italic>P.\u00a0gingivalis<\/jats:italic> can directly influence activity in trigeminal sensory neurons and this may contribute to acute and chronic inflammatory pain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13282","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T14:09:38Z","timestamp":1581689378000},"page":"846-858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["<i>Porphyromonas gingivalis<\/i> lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain"],"prefix":"10.1111","volume":"53","author":[{"given":"A.","family":"Kaewpitak","sequence":"first","affiliation":[{"name":"School of Clinical Dentistry University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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