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Human skin fibroblasts were used to examine the role of <jats:italic>T.\u2009pallidum<\/jats:italic> in modulating neurotransmitters associated with pain and to explore the signalling pathways related to neurotransmitter secretion by <jats:italic>T.\u2009pallidum<\/jats:italic> in\u00a0vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Treponema pallidum<\/jats:italic> infection did not directly lead to neuronal damage or interfere with the neuronal resting potential. Instead, it facilitated the secretion of prostaglandin E2 (PGE2) through endoplasmic reticulum stress in both rabbit and human skin fibroblasts, and upregulation of PGE2 induced the hyperpolarization of neurones. Moreover, the IRE1\u03b1\/COX\u20102 signalling pathway was identified as the underlying mechanism by which <jats:italic>T.\u2009pallidum<\/jats:italic> induced the production of PGE2 in human skin fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Treponema pallidum<\/jats:italic> promotes PGE2 secretion in skin fibroblasts, leading to the excitation of neuronal hyperpolarization and potentially contributing to the pathogenesis of painless ulcers in syphilis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19902","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T18:11:47Z","timestamp":1708452707000},"page":"1179-1190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>Treponema pallidum<\/i>\u2010induced prostaglandin <scp>E2<\/scp> secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless 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