GFAP as a marker of astrocytic damage correlated with medication overuse in migraine

Different mechanisms are involved in migraine pathogenesis, including neurogenic inflammation, neurodegenerative processes, and a potential role of microglia. The aim of this study was to assess axonal and glial damage measuring serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in migraine patients. Serum samples of 25 patients with episodic migraine (EM), 25 with chronic migraine (CM) diagnosed in accordance with the International Classification of Headache Disorders, 3rd edition (ICHD-3), and 50 age-matched healthy controls were prospectively collected. NfL and GFAP levels were assessed using ultrasensitive paramagnetic bead-based ELISA (SIMOA). Non-parametric tests were used for group comparison and 2-tailed Spearman analysis to assess correlations. GFAP levels were significantly increased in migraine patients (median 103.15 pg/mL [IQR 70.98-146.34] vs. 69.43 pg/mL [IQR 53.04-91.85], p < 0.001), particularly in those with medication overuse (106.08 [IQR 87.94-159.07] vs. 71.38 [IQR 54.16-135.06], p = 0.007), without difference between EM and CM (p = 0.985). Although NfL levels were not increased (p = 0.387), they were higher in patients with a long migraine course (rho 0.519, p < 0.001). Attack at sampling/days from last attack, migraine frequency/attack severity did not influence NfL or GFAP levels. Our findings demonstrate the occurrence of glial damage, particularly correlated with medication overuse, and the presence of axonal damage in the later disease stage, providing potential novel cues for the migraine pathogenesis.