Oxidative Stress in Migraine-Effect or Cause?

Migraine is a complex neurovascular disorder with a multifactorial pathophysiology involving genetic, metabolic, and environmental factors. Increasing evidence indicates that oxidative stress plays a key role in the development of migraine; however, it is unclear whether oxidative imbalance acts primarily as a causal factor or occurs as a consequence of migraine-related processes. Oxidative stress, defined as an imbalance between reactive oxygen species production and antioxidant defense mechanisms, contributes to neuronal hyperexcitability, mitochondrial dysfunction, and neuroinflammation-key mechanisms underlying migraine pathogenesis. Studies have shown elevated markers of oxidative damage and altered antioxidant enzyme activity in migraine patients. Simultaneously, metabolic and inflammatory changes associated with migraine may further exacerbate oxidative imbalance, suggesting a bidirectional relationship. Furthermore, genetic factors such as SOD2, GPX1, and CAT significantly influence susceptibility to oxidative stress and migraine. The CALCA gene, encoding CGRP, links oxidative stress mechanisms with neurogenic inflammation and activation of the trigeminovascular system. This article reviews the current evidence regarding the role of oxidative stress in migraine and discusses its relationship to molecular and genetic mechanisms. Particular attention is given to genes involved in oxidative pathways, mitochondrial function, and inflammatory responses, which may help explain individual susceptibility and variability in clinical presentation.