Lucchesi Cinzia, Baldacci Filippo, Cafalli Martina, Chico Lucia, Lo Gerfo Annalisa, Bonuccelli Ubaldo, Siciliano Gabriele, Gori Sara
Department of Clinical and Experimental Medicine, Institute of Neurology, University of Pisa, Pisa, Italy.
Headache. 2015 Jul-Aug;55(7):984-91. doi: 10.1111/head.12608. Epub 2015 Jun 30.
Migraine is a complex multifactorial, neurobiological disorder, whose pathogenesis is not fully understood, nor are the mechanisms associated with migraine transformation from episodic to chronic pattern. A possible role of impaired oxidative mitochondrial metabolism in migraine pathogenesis has been hypothesized, and increased levels of peripheral markers of oxidative stress have been reported in migraine patients, although the literature data are limited and heterogeneous.
The aim of this cross-sectional study was to determine plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power and total plasmatic thiol groups, all plasmatic markers related to oxidative stress, in a sample of chronic migraine patients and medication-overuse headache, compared to a control group of healthy subjects.
Thirty-three patients with a diagnosis of both chronic migraine and medication-overuse headache (International Classification of Headache Disorders,3rd edition, beta version) and 33 healthy, headache-free subjects were enrolled. Patients with comorbid/coexisting conditions were excluded, as well as patients in treatment with migraine preventive drugs. Plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power, and total thiol groups were determined in migraine patients and controls; moreover, oxidative stress biomarkers were compared in migraine patients with triptan compared to non-steroidal anti-inflammatory drug overuse.
The statistical analysis showed significantly lower levels of ferric-reducing antioxidant power and total plasmatic thiol groups, both expression of antioxidant power, in patients with chronic migraine and medication-overuse headache compared to controls (respectively, ferric antioxidant power median [interquartile range] 0.53 [0.22] vs 0.82 [0.11] mmol/L, P < .001; total thiol groups 0.25 [0.08] vs 0.51 [0.11] μmol/L, P < .001). Moreover, no statistically significant differences in oxidative stress biomarkers were detected between patients with triptan and nonsteroidal anti-inflammatory drug overuse.
The data from the present study suggest that antioxidant capacity is lower in chronic migraine patients and medication-overuse headache compared to healthy headache-free subjects, with no differences between patients with triptan or nonsteroidal anti-inflammatory drug overuse. Further investigation is certainly necessary in order to define the causal or consequential role of an imbalance between pro-oxidants and antioxidant defenses in migraine pathogenesis and "chronification" and the possible therapeutic implications in clinical practice.
偏头痛是一种复杂的多因素神经生物学疾病，其发病机制尚未完全明确，从发作性转变为慢性偏头痛的相关机制也不清楚。尽管文献数据有限且存在异质性，但已有研究推测线粒体氧化代谢受损在偏头痛发病机制中可能发挥作用，且偏头痛患者外周氧化应激标志物水平有所升高。
本横断面研究旨在测定慢性偏头痛患者和药物过量使用性头痛患者样本中与氧化应激相关的血浆晚期氧化蛋白产物、铁还原抗氧化能力和总血浆巯基水平，并与健康对照组进行比较。
纳入33例诊断为慢性偏头痛且伴有药物过量使用性头痛的患者（依据《国际头痛疾病分类》第3版，β版）和33例无头痛的健康受试者。排除患有合并症/共存疾病的患者以及正在接受偏头痛预防性药物治疗的患者。测定偏头痛患者和对照组血浆晚期氧化蛋白产物、铁还原抗氧化能力和总巯基水平；此外，比较使用曲坦类药物的偏头痛患者和非甾体抗炎药过量使用的偏头痛患者的氧化应激生物标志物。
统计分析显示，与对照组相比，慢性偏头痛患者和药物过量使用性头痛患者的铁还原抗氧化能力和总血浆巯基水平显著降低，二者均为抗氧化能力的指标（铁还原抗氧化能力中位数[四分位间距]分别为0.53[0.22]与0.82[0.11]mmol/L，P＜0.001；总巯基水平分别为0.25[0.08]与0.51[0.11]μmol/L，P＜0.001）。此外，使用曲坦类药物的患者和非甾体抗炎药过量使用的患者之间，氧化应激生物标志物未检测到统计学显著差异。
本研究数据表明，与无头痛的健康受试者相比，慢性偏头痛患者和药物过量使用性头痛患者的抗氧化能力较低，使用曲坦类药物的患者和非甾体抗炎药过量使用的患者之间无差异。为明确促氧化剂与抗氧化防御失衡在偏头痛发病机制和“慢性化”中的因果或继发作用以及在临床实践中的可能治疗意义，进一步研究必不可少。
