ReviewFrontiers in neuroscience2020
Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity.
Review in Frontiers in neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Repetitive tooth-clenching triggers kynurenine pathway activation in masseter muscle of women with temporomandibular disorders myalgia.Pain reports · 2026Article
- Characterizing the tuberculosis and type 2 diabetes mellitus comorbidity in a South African cohort using untargeted GCxGC-TOFMS metabolomics.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Recent progress in immune evasion mechanisms of triple-negative breast cancer.Journal of translational medicine · 2025Review
- Cellular and molecular characterisation of the peripheral immune environment in migraine.Pain reports · 2025Article
- Characterization of acupuncture on central amino acid metabolism based on targeted neurotransmitter analysis in mice with inflammatory pain.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Tryptophan metabolism at the crossroads of the neuro-immuno-microbial axis: implications for precision medicine in chronic diseases.Frontiers in cellular and infection microbiology · 2025Review
- The association between salivary IL-6 and poor sleep quality assessed using Apple watches in stressed workers in Japan.Scientific reports · 2024Article
- Article
- The role of metabolic reprogramming in immune escape of triple-negative breast cancer.Frontiers in immunology · 2024Review
- Effect of the novel anti-NGF monoclonal antibody DS002 on the metabolomics of pain mediators, cartilage and bone.Frontiers in pharmacology · 2024Article
- Tryptophan metabolism and small fibre neuropathy: a correlation study.Brain communications · 2024Article
- Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review.World journal of clinical cases · 2023Review
- Tetrahydrobiopterin: Beyond Its Traditional Role as a Cofactor.Antioxidants (Basel, Switzerland) · 2023Review
- Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Components of the sympathetic nervous system as targets to modulate inflammation - rheumatoid arthritis synovial fibroblasts as neuron-like cells?Journal of inflammation (London, England) · 2023Article
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- An investigation of metabolome in blood in patients with chronic peripheral, posttraumatic/postsurgical neuropathic pain.Scientific reports · 2022Article
- The Role of Kynurenine and Its Metabolites in Comorbid Chronic Pain and Depression.Metabolites · 2022Review
- Gentle Touch Therapy, Pain Relief and Neuroplasticity at Baseline in Fibromyalgia Syndrome: A Randomized, Multicenter Trial with Six-Month Follow-Up.Journal of clinical medicine · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the identification of molecular mechanisms associated with pain persistence, no significant therapeutic improvements have been made. Advances in the understanding of the molecular mechanisms that induce pain hypersensitivity will allow the development of novel, effective, and safe therapies for chronic pain. Various pro-inflammatory cytokines are known to be increased during chronic pain, leading to sustained inflammation in the peripheral and central nervous systems. The pro-inflammatory environment activates additional metabolic routes, including the kynurenine (KYN) and tetrahydrobiopterin (BH4) pathways, which generate bioactive soluble metabolites with the potential to modulate neuropathic and inflammatory pain sensitivity. Inflammation-induced upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) and guanosine triphosphate cyclohydrolase I (GTPCH), both rate-limiting enzymes of KYN and BH4 biosynthesis, respectively, have been identified in experimental chronic pain models as well in biological samples from patients affected by chronic pain. Inflammatory inducible KYN and BH4 pathways upregulation is characterized by increase in pronociceptive compounds, such as quinolinic acid (QUIN) and BH4, in addition to inflammatory mediators such as interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). As expected, the pharmacologic and genetic experimental manipulation of both pathways confers analgesia. Many metabolic intermediates of these two pathways such as BH4, are known to sustain pain, while others, like xanthurenic acid (XA; a KYN pathway metabolite) have been recently shown to be an inhibitor of BH4 synthesis, opening a new avenue to treat chronic pain. This review will focus on the KYN/BH4 crosstalk in chronic pain and the potential modulation of these metabolic pathways that could induce analgesia without dependence or abuse liability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.