Journal Article Epublish
PubMed: 41682889 DOI: 10.3390/jcm15031208
Neurochemical Changes Following Botulinum Toxin Type A in Chronic Migraine: An LC-MS/MS and HPLC Evaluation of Plasma and Urinary Biomarkers.
J Clin Med 15(3)
Authors: Seyma Dumur, Demet Aygun, Era Gorica, Hafize Boyaci, Bagnu Dundar, Dildar Konukoglu, Hafize Uzun
Affiliations
- Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34203 Istanbul, Turkey.
- Department of Neurology, Faculty of Medicine, Istanbul Atlas University, 34203 Istanbul, Turkey.
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zürich, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland.
- Department of Cardiac Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
- Fikret Biyal Central Biochemistry Laboratory, Istanbul University-Cerrahpasa, 34303 Istanbul, Turkey.
- Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey.
Abstract
Background: Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraine (CM), yet the accompanying neurochemical changes remain incompletely characterized. Objective: To evaluate the effects of BoNT-A on plasma substance P (SP), γ-aminobutyric acid (GABA), glutamate, glutamine, and 5-hydroxytryptamine (5-HT), and on urinary 5-HT, and to explore relationships with clinical outcomes. Methods: In this prospective study, plasma neurotransmitters were analyzed in CM patients (n = 31) at baseline and one month after BoNT-A (155 U; PREEMPT protocol) and in healthy controls (n = 30). Plasma SP was measured using enzyme-linked immunosorbent assay (ELISA); plasma GABA, glutamate, and glutamine were quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS) with isotopically labeled internal standards; plasma and urinary 5-HT were determined by high-performance liquid chromatography (HPLC). Clinical outcomes included monthly headache frequency, Visual Analog Scale (VAS), and Migraine Disability Assessment (MIDAS). Statistical analyses applied appropriate parametric or non-parametric tests with p < 0.05 considered significant. Results: One month post-BoNT-A, headache frequency, MIDAS, and VAS were significantly reduced (all p < 0.001). SP levels were significantly higher after BoNT-A than at baseline and versus controls. Plasma 5-HT increased post-BoNT-A, while urinary 5-HT decreased. Plasma GABA was elevated in patients versus controls without statistical significance. Glutamine was significantly higher before treatment, whereas the Glu/Gln ratio increased after BoNT-A. Correlations revealed that higher GABA was associated with lower VAS and attack frequency post-treatment. Conclusions: BoNT-A provided short-term clinical improvement with distinct neurochemical changes, including increased plasma SP and 5-HT, decreased urinary 5-HT, reduced glutamine, and a higher Glu/Gln ratio. These biomarkers, particularly Glu/Gln, may serve as indicators of cortical excitability and therapeutic response in CM.
MeSH
Headache, Migraine Disorders, Enzyme-Linked Immunosorbent Assay, Biomarkers, Botulinum Toxins, Type A, Botulinum Toxins, Therapeutics, Glutamine, Plasma