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Lookup NU author(s): Dr Jamie Coulter, Dr Christopher NileORCiD, Professor John Whitworth, Professor Ruth ValentineORCiD, Dr Chien-Yi ChangORCiD, Dr Seva TelezhkinORCiD, Professor Justin DurhamORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Introduction: Current therapeutic practices have limited effectiveness at targeting acute pain locally. This is in part due to the lack of understanding of the neuroinflammatory pathways active within pulpitis. Increased activity of indoleamine 2,3 dioxygenase (IDO) was linked to hypersensitivity and pain in several settings. IDO is the rate limiting enzyme of the kynurenine pathway, however, changes in IDO’s activity and expression in pulpitis have not been investigated. Methods: 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 examined using high-performance liquid chromatography (HPLC), qPCR, and immunocytochemistry (ICC). Subsequently, ‘odontoblast-like cells’ (OLCs) derived from dental pulp stem cells were stimulated in vitro with bacterial lipopolysaccharide (LPS) and a synthetic proxy for DNA cytosine-phosphate-guanine (CpG) oligonucleotide 2006 (ODN 2006). Effects of these compounds on levels and transcription of markers of the KYN pathway were then analysed by qPCR and HPLC-mass spectrometry. Results: IDO activity was significantly raised in SIP compared with healthy controls. ICC fluorescent imaging showed that IDO and KYN were co-localised with the markers of macrophages and neuronal fibres. qPCR data of SIP indicated that increased IDO may direct the KYN pathway towards 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. Conclusions: This manuscript is to our knowledge the first to demonstrate links between IDO activity, neuroinflammation and algogenic pathways in SIP and localise this process to neuronal fibres. 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 neuro-excitatory metabolites in vivo
Author(s): Coulter J, Nile C, Lemos H, LoCoco P, Whitworth J, Valentine R, Diogenes A, Chang C, Mellor A, Telezhkin V, Durham J
Publication type: Article
Publication status: Published
Journal: Journal of Dental Research
Year: 2026
Pages: Epub ahead of print
Online publication date: 08/03/2026
Acceptance date: 21/12/2025
Date deposited: 22/12/2025
ISSN (print): 0022-0345
ISSN (electronic): 1544-0591
Publisher: Sage Publications Ltd
URL: https://doi.org/10.1177/00220345261416437
DOI: 10.1177/00220345261416437
Data Access Statement: Data are available on Figshare (https://figshare.com/s/d0c27198cfb1d3602ed5) and shared with reviewers.
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