Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis

Blau theorized that migraine triggers are exposures that in higher amounts would damage the brain. The recent discovery that the TRPA1 ion channel transduces oxidative stress and triggers neurogenic inflammation suggests that oxidative stress may be the common denominator underlying migraine triggers.

The aim of this review is to present and discuss the available literature on the capacity of common migraine triggers to generate oxidative stress in the brain.

A Medline search was conducted crossing the terms "oxidative stress" and "brain" with "alcohol," "dehydration," "water deprivation," "monosodium glutamate," "aspartame," "tyramine," "phenylethylamine," "dietary nitrates," "nitrosamines," "noise," "weather," "air pollutants," "hypoglycemia," "hypoxia," "infection," "estrogen," "circadian," "sleep deprivation," "information processing," "psychosocial stress," or "nitroglycerin and tolerance." "Flavonoids" was crossed with "prooxidant." The reference lists of the resulting articles were examined for further relevant studies. The focus was on empirical studies, in vitro and of animals, of individual triggers, indicating whether and/or by what mechanism they can generate oxidative stress.

In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Depending on the trigger, mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

Oxidative stress is a plausible unifying principle behind the types of migraine triggers encountered in clinical practice. The possible implications for prevention and for understanding the nature of the migraine attack are discussed.