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Targeted liquid chromatography-tandem mass spectrometry profiling of arginine and histidine derivatives in chronic migraine: Discriminatory performance and changes after onabotulinumtoxinA therapy

Dumur S, Diarra K, Sewidan J, Kalmoni JJ, Aygun D, Konukoglu D, Uzun H

Headache, 2026

30 participants

Abstract

OBJECTIVE: This study was conducted to characterize plasma arginine, histidine, 1-methylhistidine, and 3-methylhistidine in chronic migraine and to evaluate their discriminatory ability and association with early clinical response to onabotulinumtoxinA (BoNT-A).

BACKGROUND: Alterations in nitric oxide- and histamine-related metabolic pathways may contribute to chronic migraine biology and may provide circulating biomarkers for disease stratification and treatment monitoring. Targeted liquid chromatography-tandem mass spectrometry profiling enables precise quantification of candidate amino acids and derivatives implicated in these pathways.

METHODS: This retrospective secondary analysis was conducted as a case-control study with an embedded uncontrolled pre-post analysis and included 30 adults with chronic migraine receiving BoNT-A and 30 age- and sex-matched healthy controls from Istanbul Atlas University Hospital, based on clinical and laboratory data collected between May 15, 2023, and December 15, 2024. Plasma arginine, histidine, 1-methylhistidine, and 3-methylhistidine were quantified by liquid chromatography-tandem mass spectrometry. In the chronic migraine group, pain intensity (visual analog scale [VAS]) and monthly migraine attack frequency were assessed at baseline and 1 month after BoNT-A. Between-group comparisons and within-subject pre-post comparisons were performed, and exploratory analyses evaluated relationships between metabolite levels and clinical…

How strong is the evidence?

Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 30 participants or records.

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