Determining the Serum Proteomic Profile in Migraine Patients with LC–MS

A joint study between Peking University and Peking University People’s Hospital both in China set out toanalyze the serum proteome of migraine patients and healthy controls and identify differentially expressed proteins. The research team believes that this may provide a reference for the study of biomarkers and pathophysiological mechanisms of migraine. To carry out the analysis, they employed liquid chromatography–mass spectrometry (LC–MS). The results of their study were published in Frontiers in Molecular Neuroscience (1).

A common ailment worldwide, the global prevalence of migraine is 14.7%, with the Chinese annual prevalence reported to be 9.3% (2). A paroxysmal headache disorder characterized by reoccurring, mostly unilateral, pulsating, moderate-to-severe headaches, often accompanied by nausea, vomiting, photophobia, and phonophobia, which may also have vision, sensory, or other kinds of aura, patients suffering from migraine can experience headaches for 4 to 72 h either without treatment or with ineffective treatment (3). The prevalence of migraine in women is two to three times greater than in men, with the highest prevalence occurring in those between the ages of 25 and 55 years of age (1). According to the 2021 Global Burden of Disease Study by the World Health Organization, migraine was the world’s third most disabling disease related to neurological disorders, seriously affecting the sufferers’ quality of life (4).

The pathophysiology of migraine is still not completely understood. While there are generally accepted mechanisms that may play a role in a migraine attack, including cortical spreading depression, alteration in thalamocortical circuits, altered brain connectivity, and sensitization of the trigemino-cervical complex, migraine diagnosis at present depends on the patient’s clinical history (5). While well-accepted diagnostic criteria are in place, migraine is still a complex disorder that remains underdiagnosed and misdiagnosed, with the lack of appropriate biomarkers an obstacle to developing more effective diagnostic criteria and treatments (6).

Few proteomics studies at present have been developed to identify biomarkers and pathophysiological mechanisms associated with migraine. Researchers at Leiden University Medical Center (Leiden, the Netherlands), focusing on the cortical synapse proteomics of a transgenic migraine mouse model with mutated CaV2.1 calcium in their study, observed upregulated proteins in the mutant mice related to neurite outgrowth and actin dynamics, vesicle turnover, and glutamate transporters (7). A study conducted at Case Western Reserve University (Cleveland, Ohio) compared the protein expression of the zygomaticotemporal branch of the trigeminal nerve in patients with and without migraine headaches and found five significant pathways involved in cytoskeletal organization, myelination of axons, and nervous system development (8). Two papers stemming from research conducted at the University of Modena and Reggio Emilia in Modena, Italy, examined the serum and urinary proteome of women suffering from menstrual-related migraine and post-menopause migraine, in the search for potential biomarkers (9,10). The researchers of the current study were motivated by the lack of studies comparing the serum proteome of migraine patients and healthy controls to identify differentially expressed proteins that could serve as potential biomarkers for more accurate diagnosis and treatment of migraine (1).

Twenty-seven migraine patients and 20 healthy people matching the age and sex ratio of the migraine group were collected. A total of 27 differential proteins between migraine patients and healthy controls were identified in this study by LC–MS; eight of these proteins belong to the component of immunoglobulins, and C1QA, LBP, HRG, ORM1, and SAA4 are also related to inflammation and immunity. The differential proteins between the ictal and the interictal groups are also related to inflammation and immunity, which the researchers state suggests that neuroinflammation and immune disorders may participate in the pathophysiological mechanism of migraine (1).

The differential expression of certain proteins related to inflammation, immune response, and energy metabolism implies that the pathogenesis of migraine might be related to inflammation, immunity, and energy metabolism disorders; the team hopes to research specific molecular mechanisms in the future (1).

Migraine Headache. © Artem Furman - stock.adobe.com

References

1. Han, Y.; Wang, Y.; Zou, X.; et al. The Serum Proteomic Profile in Patients with Migraine. Front. Mol. Neurosci. 2025, 18, 1460403. DOI: 10.3389/fnmol.2025.1460403

2. Yu, S. Y.; Cao, X. T.; Zhao, G.; et al. The Burden of Headache in China: Validation of Diagnostic Questionnaire for a Population-Based Survey. J. Headache Pain 2011, 12 (2), 141–146. DOI: 10.1007/s10194-011-0336-2

3. Zhang, Y.; Kong, Q.; Chen,J.; et al. International Classification of Headache Disorders 3rd Edition Beta-Based Field Testing of Vestibular Migraine in China: Demographic, Clinical Characteristics, Audiometric Findings and Diagnosis Statues. Cephalalgia 2015, 36 (3), 240–248. DOI: 10.1177/0333102415587704

4. GBD 2021 Nervous System Disorders Collaborators. Global, Regional, and National Burden of Disorders Affecting the Nervous System, 1990-2021: A Systematic Analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024, 23 (4), 344–381. DOI: 10.1016/S1474-4422(24)00038-3

5. Charles, A. The Pathophysiology of Migraine: Implications for Clinical Management. Lancet Neurol. 2018, 17 (2), 174–182. DOI: 10.1016/S1474-4422(17)30435-0

6. Durham, P.; Papapetropoulos, S. Biomarkers Associated with Migraine and their Potential Role in Migraine Management. Headache 2013, 53 (8),1262–1277. DOI: 10.1111/head.12174

7. Klychnikov, O. I.; Li, K. W.; Sidorov, I. A.; et al. Quantitative Cortical Synapse Proteomics of a Transgenic Migraine Mouse Model with Mutated Ca(V)2.1 Calcium Channels. Proteomics 2010, 10 (13), 2531–2535. DOI: 10.1002/pmic.200900733

8. Guyuron, B.; Yohannes, E.; Miller, R.; et al. Electron Microscopic and Proteomic Comparison of Terminal Branches of the Trigeminal Nerve in Patients with and without Migraine Headaches. Plast. Reconstr. Surg. 2014, 134 (5), 796e–805e. DOI: 10.1097/PRS.0000000000000696

9. Bellei, E.; Rustichelli, C.; Bergamini, S.; et al. Proteomic Serum Profile in Menstrual-Related and Post Menopause Migraine. J. Pharm. Biomed. Anal. 2020, 184, 113165. DOI: 10.1016/j.jpba.2020.113165

10. Bellei, E.; Bergamini, S.; Rustichelli, C.; et al. Urinary Proteomics Reveals Promising Biomarkers in Menstrually Related and Post-Menopause Migraine. J. Clin. Med. 2021, 10 (9),1854. DOI: 10.3390/jcm10091854