ArticleFrontiers in neuroscience2020
Kynurenine, Tetrahydrobiopterin, and Cytokine Inflammatory Biomarkers in Individuals Affected by Diabetic Neuropathic Pain.
Article in Frontiers in neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05896878 (The Effects of Daily Anti-inflammatory Supplementation on Foundation Pain Index Scores in Chronic Opiate Patients), which is not on this map. Cited by 22 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effects of Daily Anti-inflammatory Supplementation on Foundation Pain Index Scores in Chronic Opiate Patients
Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat (Diabetes Metab J 2025;49:990-1005).Diabetes & metabolism journal · 2025Article
- Cellular and molecular characterisation of the peripheral immune environment in migraine.Pain reports · 2025Article
- Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat.Diabetes & metabolism journal · 2025Article
- Serum Metabolomic Profiling Reveals Differences Between Systemic Sclerosis Patients with Polyneuropathy.International journal of molecular sciences · 2025Article
- Role of microbiota in pain: From bench to bedside.iMetaOmics · 2025Review
- Blood metabolomic profile in patients with type 2 diabetes mellitus with diabetic peripheral neuropathic pain.Journal of diabetes investigation · 2025Article
- Beyond inflammation: the multifaceted therapeutic potential of targeting the CXCL8-CXCR1/2 axis in type 1 diabetes.Frontiers in immunology · 2025Review
- Neuroactive Kynurenine Metabolite Alterations Unveil Novel Association to Locomotor Deterioration in Diabetic Neuropathy.International journal of tryptophan research : IJTR · 2025Article
- Activation of the kynurenine pathway identified in individuals with covert hepatic encephalopathy.Hepatology communications · 2024Article
- Dysregulation of tetrahydrobiopterin metabolism in myalgic encephalomyelitis/chronic fatigue syndrome by pentose phosphate pathway.Journal of central nervous system disease · 2024Article
- Correlation between Neutrophil-to-Lymphocyte Ratio and Diabetic Neuropathy in Chinese Adults with Type 2 Diabetes Mellitus Using Machine Learning Methods.International journal of endocrinology · 2024Article
- Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.Molecules (Basel, Switzerland) · 2023Review
- Tetrahydrobiopterin: Beyond Its Traditional Role as a Cofactor.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Editorial: Insights in experimental pharmacology and drug discovery: 2022.Frontiers in pharmacology · 2023Article
- Stability Studies of Kynurenine Pathway Metabolites in Blood Components Define Optimal Blood Processing Conditions.International journal of tryptophan research : IJTR · 2023Article
- 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
- Kynurenines in the Pathogenesis of Peripheral Neuropathy During Leprosy and COVID-19.Frontiers in cellular and infection microbiology · 2022Review
- A Review of the Clinical and Therapeutic Implications of Neuropathic Pain.Biomedicines · 2021Review
- T lymphocyte and monocyte subsets are dysregulated in type 1 diabetes patients with peripheral neuropathic pain.Brain, behavior, & immunity - health · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropathic pain is a common complication of diabetes with high morbidity and poor treatment outcomes. Accumulating evidence suggests the immune system is involved in the development of diabetic neuropathy, whilst neuro-immune interactions involving the kynurenine (KYN) and tetrahydrobiopterin (BH4) pathways have been linked to neuropathic pain pre-clinically and in several chronic pain conditions. Here, using a multiplex assay, we quantified serum levels of 14 cytokines in 21 participants with type 1 diabetes mellitus, 13 of which were classified as having neuropathic pain. In addition, using high performance liquid chromatography and gas chromatography-mass spectrometry, all major KYN and BH4 pathway metabolites were quantified in serum from the same cohort. Our results show increases in GM-CSF and IL-8, suggesting immune cell involvement. We demonstrated increases in two inflammatory biomarkers: neopterin and the KYN/TRP ratio, a marker of indoleamine 2,3-dioxygenase activity. Moreover, the KYN/TRP ratio positively correlated with pain intensity. Total kynurenine aminotransferase activity was also higher in the diabetic neuropathic pain group, indicating there may be increased production of the KYN metabolite, xanthurenic acid. Overall, this study supports the idea that inflammatory activation of the KYN and BH4 pathways occurs due to elevated inflammatory cytokines, which might be involved in the pathogenesis of neuropathic pain in type 1 diabetes mellitus. Further studies should be carried out to investigate the role of KYN and BH4 pathways, which could strengthen the case for therapeutically targeting them in neuropathic pain conditions.
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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.