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Serum calcitonin gene-related peptide and inflammatory marker dynamics across the migraine attack cycle: A case-control analysis

Articles in Press

Document Type : Original Article

Authors

1 Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Headache Department, Neurology Ward, Sina University Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Molecular Genetics, School of Biological Sciences, Kharazmi University, Tehran, Iran

3 Department of Clinical Nutrition, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

4 Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Clinical Nutrition and Dietetics, School of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Department of Nutrition, School of Medical Sciences and Technologies, Science and Research Branch, Islamic Azad University, Tehran, Iran

Abstract

Background: The role of calcitonin gene-related peptide (CGRP) and inflammatory pathways in migraine pathophysiology remains to be fully elucidated. This study addressed inconsistencies in the existing literature by comparing serum levels of CGRP and inflammatory markers in patients with migraine during (ictal) and between (interictal) attacks, relative to healthy controls.
Methods: A total of 169 individuals were enrolled: 39 patients with chronic migraine (CM), 100 with episodic migraine (EM), and 30 healthy controls matched for age and sex. Among patients with EM, 63 were assessed during a migraine attack, while 37 were assessed during an interictal phase. Following assessment of demographic and headache characteristics, venous blood samples were obtained. 
Serum levels of CGRP, cyclooxygenase-2 (COX-2), and interleukin-17 (IL-17) were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits.
Results: The mean age of the control group and patients with migraine was 41 and 38 years, respectively. Patients with EM in the ictal phase exhibited significantly higher serum CGRP and IL-17 levels compared to interictal patients and healthy controls (P < 0.001). Patients with CM also had significantly higher serum concentrations of CGRP and IL-17 than both interictal EM patients and healthy controls (P < 0.01). Analysis of serum COX-2 levels also revealed that both the CM and ictal EM groups had significantly higher concentrations than the interictal EM group (P < 0.001).
Conclusion: Our findings indicate that both the ictal state in EM and the CM state are characterized by significant, similar increases in serum levels of CGRP, IL-17, and COX-2, distinguishing them from both the interictal state and healthy controls.

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Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 29 June 2026
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