ArticleJournal of neuroinflammation2025
IDO1 modulates pain sensitivity and comorbid anxiety in chronic migraine through microglial activation and synaptic pruning.
Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The mechanism of different microglial receptors mediating central inflammation in chronic migraine: a meta-analysis.The journal of headache and pain · 2026Pooled it
- Article
- TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Dexmedetomidine Alleviates Visceral Pain by Modulating a Pro-Inflammatory Macrophage-Associated Gene Network.Biomedicines · 2026Article
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Temporal Transcriptomic Changes in the Cingulate Cortex of Neuropathic Pain Mice.Biomedicines · 2026Article
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- SP1 recruits TET1 to mediate Kif1a demethylation and synaptic remodeling in a mouse model of chronic migraine.The journal of headache and pain · 2026Article
- The pPVTThe journal of headache and pain · 2026Article
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Inhibition of the METTL3/mThe journal of headache and pain · 2025Article
- Leveraging Fiber Photometry to Decipher Neural Circuits Underlying Anxiety in Mice.Fundamental & clinical pharmacology · 2025Review
- Anxiolytic Effects of Natural Products: Pathological Mechanisms, Molecular Targets, Therapeutic Prospects.Neuropsychiatric disease and treatment · 2025Review
- The gut-brain-circadian axis in anxiety and depression: a critical review.Frontiers in psychiatry · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundChronic migraine is a prevalent and potentially debilitating neurological disorder that is often comorbid with mental health conditions (such as anxiety and depression), but the underlying mechanisms linking these conditions remain poorly understood. Indoleamine 2,3-dioxygenase 1 (IDO1) has been implicated in inflammatory processes, including neuroinflammation and pain. However, its role as a link between neuroinflammation and pain sensitization in chronic migraine is not well defined.
methodsMale mice were used to establish a model of chronic migraine by recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg). Using pharmacological approaches, transgenic strategies and adeno-associated virus (AAV) intervention, we investigated the role of IDO1 in pain sensitization and migraine-related mood disorders in an NTG-induced chronic migraine mouse model. We employed a combination of immunoblotting, immunohistochemistry, three-dimensional reconstruction, RNA sequencing, electrophysiology, in vivo fiber photometry, and behavioral assays to elucidate the underlying mechanisms involved.
resultsOur findings demonstrated that pharmacological inhibition and genetic knockout of IDO1 significantly alleviated pain sensitivity in a chronic migraine model. Neuronal activity in the anterior cingulate cortex (ACC) was evaluated with in vitro c-Fos immunostaining as well as in vivo fiber photometry, and a shift in the excitation/inhibition (E/I) balance toward excitation was observed through whole-cell patch clamp recording. Notably, IDO1 expression was increased in the ACC, and AAV-mediated IDO1 knockdown in the ACC rescued pain sensitivity, electrophysiological E/I balance changes, and anxiety-like behavior in chronic migraine model mice. Furthermore, IDO1 regulated microglial activation and pruning of neuronal synapses in the ACC. IDO1's microglial pruning function appears to be mediated through the interferon (IFN) signaling pathway, and the behavioral changes induced by IDO1 knockdown in the ACC could be reversed by activating this pathway.
conclusionsOur findings revealed that microglial IDO1 in the ACC drives pain sensitization and anxiety in chronic migraine, highlighting IDO1 as a potential therapeutic target for chronic migraine treatment.
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