SynthesisFrontiers in immunology2026
Mapping the immune and epigenetic landscape of medication-overuse headache (MOH): a systematic review.
Synthesis in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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
4 citing papers in PubMed.
- Dopaminergic Dysregulation in Migraine: From Hypothalamic A11 Dysfunction to a Systemic Biobehavioral Phenotype.International journal of molecular sciences · 2026Review
- Whole blood DNA methylation signature of epigenetic aging in medication overuse headache.The journal of headache and pain · 2026Article
- CGRP at the Neuroimmune Interface: Regulator of Host Defense, Tumor Immunity, and Tissue Homeostasis.Research (Washington, D.C.) · 2026Review
- Caffeine use disorder and analgesic dependence in medication-overuse headache: insights into an underrecognized relationship.Frontiers in neurologyArticle
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Medication-overuse headache (MOH) develops when drugs intended for acute pain relief lower the threshold for headache chronification. The biological mechanisms driving this transition remain poorly understood. We aim to synthesize current evidence on immune and epigenetic alterations in MOH, identifying new targets of interest and outlining priorities for future research and precision-based interventions. Methods: We systematically searched PubMed, Embase and Scopus from inception to May 2025 for original human or animal studies reporting immune and/or epigenetic measures in MOH. Risk of bias (RoB) was assessed with the SYRCLE tool for animal studies and JBI tools for human studies. Findings were narratively synthesized, and a domain-based strength-of-evidence (SoE) framework was applied. Results: Thirteen studies met inclusion criteria. Animal studies identified two immunological pathways involved in MOH resolution: low-dose interleukin-2-mediated expansion of regulatory T cells and inhibition of the P2X purinoceptor 7 (P2X7R)/NLRP3 inflammasome signaling. Clinical studies reported systemic low-grade inflammation in MOH patients, including elevated leukocyte counts, interleukin-6 and gut-derived inflammatory markers. Two epigenetic studies identified differential DNA methylation in genes regulating immune responses and pain transmission. Most studies were small and cross-sectional with limited adjustment. Overall SoE was low-moderate across domains. Conclusion: Current evidence points to plausible immune and epigenetic involvement in MOH but is insufficient for causal inference or clinical guidance. Findings are hypothesis-generating and most useful for translational prioritization.
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