Carta Sara, Chiodega Vanessa, Tiberi Riccardo, Pasquali Alessia, Ferrari Sergio, Bozzetti Silvia, Ranieri Federico, Marchioretto Fabio, Mariotto Sara
Department of Neurosciences, Biomedicine and Movement Sciences, Neurology Unit, University of Verona, Policlinico GB Rossi, P.Le LA Scuro 10, Verona, 37135, Italy.
Experimental and Clinical Medicine Department, Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
Immunol Res. 2025 Aug 9;73(1):119. doi: 10.1007/s12026-025-09674-x.
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.
偏头痛的发病机制涉及多种不同的机制，包括神经源性炎症、神经退行性过程以及小胶质细胞的潜在作用。本研究的目的是通过检测偏头痛患者血清中神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）的水平来评估轴突和胶质细胞损伤。前瞻性收集了25例发作性偏头痛（EM）患者、25例根据《国际头痛疾病分类》第三版（ICHD-3）诊断的慢性偏头痛（CM）患者以及50例年龄匹配的健康对照者的血清样本。使用基于超灵敏顺磁珠的酶联免疫吸附测定法（SIMOA）评估NfL和GFAP水平。采用非参数检验进行组间比较，并使用双尾Spearman分析评估相关性。偏头痛患者的GFAP水平显著升高（中位数103.15 pg/mL [四分位间距70.98 - 146.34] 对比69.43 pg/mL [四分位间距53.04 - 91.85]，p < 0.001），特别是在药物过度使用的患者中（106.08 [四分位间距87.94 - 159.07] 对比71.38 [四分位间距54.16 - 135.06]，p = 0.007），EM和CM之间无差异（p = 0.985）。虽然NfL水平未升高（p = 0.387），但在偏头痛病程较长的患者中较高（rho 0.519，p < 0.001）。采样时的发作/距上次发作天数、偏头痛频率/发作严重程度均不影响NfL或GFAP水平。我们的研究结果表明存在胶质细胞损伤，特别是与药物过度使用相关，并且在疾病后期存在轴突损伤，为偏头痛的发病机制提供了潜在的新线索。
