Introduction: Migraine is a common primary headache disorder associated with neuronal excitability, trigeminovascular activation, and neuroendocrine responses. Magnesium, cyclic adenosine monophosphate (cAMP), adrenocorticotropic hormone (ACTH), and cortisol may contribute to migraine biology. This study aimed to evaluate these markers in patients with migraine during ictal and interictal periods. Methods: This case-control study included 40 patients with migraine and 20 healthy controls. Migraine was diagnosed according to the International Headache Society criteria. Blood samples were obtained from migraine patients during both ictal and interictal periods and once from healthy controls. Serum magnesium, plasma ACTH, serum cortisol, and plasma cAMP levels were measured. Results: Serum magnesium levels were significantly lower in migraine patients during both ictal and interictal periods compared with controls (0.74 ± 0.16 and 0.74 ± 0.11 vs. 0.87 ± 0.11 mmol/L, p<0.005). Plasma ACTH levels were significantly higher during both periods compared with controls (39.65 ± 27.35 and 39.07 ± 19.04 vs. 24.53 ± 6.54 pg/mL, p<0.005). Plasma cAMP levels were also significantly higher in migraine patients (5.57 ± 1.73 and 5.73 ± 2.42 vs. 4.68 ± 1.41 pmol/mL, p<0.05). Serum cortisol levels did not differ significantly. A negative correlation was found between ACTH and cortisol levels in migraine patients. Conclusion: These findings suggest that migraine may be associated with persistent alterations in magnesium status, cyclic nucleotide activity, and hypothalamic-pituitary-adrenal axis regulation. The presence of similar biochemical changes during both ictal and interictal periods supports the concept that migraine is not limited to acute attacks but may reflect an underlying biological susceptibility.
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Karadağ et al. (2026) studied this question.
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