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This is in part due to the lack of understanding of the neuroinflammatory pathways active within pulpitis. Increased activity of inadoleamine 2,3 dioxygenase (IDO) was linked to hypersensitivity and pain in several settings. IDO is the rate-limiting enzyme of the kynurenine pathway, but changes in IDO\u2019s activity and expression in pulpitis have not been investigated. Tooth samples with a diagnosis of symptomatic irreversible pulpitis (SIP) were collected, and levels and activity of IDO and other markers of the kynurenine (KYN) pathway were examined using high-performance liquid chromatography (HPLC), quantitative polymerase chain reaction (PCR), and immunocytochemistry (ICC). Subsequently, odontoblast-like cells (OLCs) derived from dental pulp stem cells were stimulated in vitro with bacterial lipopolysaccharide and a synthetic proxy for DNA cytosine-phosphate-guanine (CpG) oligonucleotide 2006 (ODN 2006). The effects of these compounds on KYN pathway marker levels and transcription were then analyzed using quantitative PCR and HPLC mass spectrometry. IDO activity was significantly raised in SIP compared with healthy controls. ICC fluorescent imaging showed that IDO and KYN were colocalized with the markers of macrophages and neuronal fibers. Quantitative PCR data of SIP indicated that increased IDO may direct the KYN pathway toward the generation of the neuroinflammatory catabolite quinolinic acid, a metabolite that is opposite to the production of neuroprotective kynurenic acid. Administration of OLCs with ODN 2006 in vitro induced changes similar to those developed in SIP induced by bacterial infection. To our knowledge, this article is the first to demonstrate links between IDO activity, neuroinflammation, and algogenic pathways in SIP and localize this process to neuronal fibers. These observations highlight the potential role of the kynurenine pathway in SIP, but further investigation is required to determine if these changes are mirrored in the levels of neuroexcitatory metabolites in vivo.<\/jats:p>","DOI":"10.1177\/00220345261416437","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:23:56Z","timestamp":1773224636000},"page":"1482-1491","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of the Kynurenine Pathway in Irreversible Pulpitis"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6328-7702","authenticated-orcid":false,"given":"J.","family":"Coulter","sequence":"first","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.J.","family":"Nile","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Lemos","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"LoCoco","sequence":"additional","affiliation":[{"name":"University of Texas at San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Whitworth","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.A.","family":"Valentine","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Diogenes","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-4019","authenticated-orcid":false,"given":"C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mellor","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Telezhkin","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Durham","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_3_2_2_1","unstructured":"AAE. 2013. 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