ArticleThe Journal of clinical investigation2012
Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
170 citing papers in PubMed, 1 synthesis or guideline pooled it, 314 citations in OpenAlex.
- Sexually Dimorphic Neuroimmune Pathways in Chronic Pain: A Comprehensive Systematic Review of Cellular and Molecular Mechanisms.Biomolecules · 2026Pooled it
- Impact of Nano-Selenium supplementation on the JAK/STAT signaling pathway in major depressive disorder: a Triple-Blind, randomized controlled trial.BMC psychiatry · 2025Trial
- Plasma inflammatory cytokines and treatment-resistant depression with comorbid pain: improvement by ketamine.Journal of neuroinflammation · 2021Trial
- Cost-utility and biological underpinnings of Mindfulness-Based Stress Reduction (MBSR) versus a psychoeducational programme (FibroQoL) for fibromyalgia: a 12-month randomised controlled trial (EUDAIMON study).BMC complementary and alternative medicine · 2016Trial
- Noncanonical NF-κB activation mediates STAT3-stimulated IDO upregulation in myeloid-derived suppressor cells in breast cancer.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- The role of the kynurenine pathway in the pathogenesis of pain and affective disorders after traumatic brain injury.Brain, behavior, & immunity - health · 2026Review
- A Functional SNP in the Promoter Region of Ovine IDO2 Associated With Melatonin Levels via Affecting Transcription Activity by CLOCK.Animal genetics · 2026Article
- Low 5HTJournal of neurochemistry · 2026Review
- Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress.Journal of neuroinflammation · 2026Review
- Interleukins in Major Depressive Disorder: Lessons From Autoimmune Diseases and Pathways to Clinical Translation.CNS neuroscience & therapeutics · 2026Review
- Indoleamine 2,3-Dioxygenase: A Potential Biomarker for Neural Damage Severity of Leprosy Neuropathy.Cellular and molecular neurobiology · 2026Article
- Synaptic plasticity in affective comorbidities of neuropathic pain: a bibliometric analysis based on WoSCC and PubMed (2003-2025).Frontiers in neurology · 2026Article
- Rewiring the Lung-CNS Axis After Spinal Cord Injury.Journal of inflammation research · 2026Review
- Stratifying the Inflamed Endotype in Difficult-to-Treat Depression: A Roadmap from Biomarkers to Precision Immunopsychiatry.Clinical neuropsychiatry · 2025Article
- Association Between Circulating Cytokines and Psychosomatic Syndromes in Patients with Mood Disorders.Clinical neuropsychiatry · 2025Article
- Refining the adjuvant-induced rat model of monoarthritis by optimizing the induction volume and injection site.Scientific reports · 2025Article
- Design, Synthesis, and Biological Evaluation of Dual Functional Inhibitors Targeting Indoleamine 2,3-dioxygenase 1 (IDO1) and Tryptophan 2,3-dioxygenase (TDO).ACS medicinal chemistry letters · 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
- The Pathogenesis and Medical Treatment of Depression: Opportunity and Challenge.Neurology international · 2025Review
- GAPDH heme delivery to Indoleamine 2,3-dioxygenase 1 involves their complex formation and complementary charge pairing at the protein-protein interface.The Journal of biological chemistry · 2025Article
110 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Pain and depression are frequently comorbid disorders, but the mechanism underlying this association is unknown. Here, we report that brain indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in this comorbidity. We found that chronic pain in rats induced depressive behavior and IDO1 upregulation in the bilateral hippocampus. Upregulation of IDO1 resulted in the increased kynurenine/tryptophan ratio and decreased serotonin/tryptophan ratio in the bilateral hippocampus. We observed elevated plasma IDO activity in patients with both pain and depression, as well as in rats with anhedonia induced by chronic social stress. Intra-hippocampal administration of IL-6 in rats, in addition to in vitro experiments, demonstrated that IL-6 induces IDO1 expression through the JAK/STAT pathway. Further, either Ido1 gene knockout or pharmacological inhibition of hippocampal IDO1 activity attenuated both nociceptive and depressive behavior. These results reveal an IDO1-mediated regulatory mechanism underlying the comorbidity of pain and depression and suggest a new strategy for the concurrent treatment of both conditions via modulation of brain IDO1 activity.
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What OpenQuestion holds
Registered trials
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.