Impaired oxidative-antioxidative balance during migraine attack

Reduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N‐acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham‐Controlled Pilot Study

“…To our knowledge, this is the first randomized, sham‐controlled trial of a combined antioxidant based on NEC and the only study of NAc in migraine prevention. In 2010, Visser 65 proposed trialing Vit C and NAc for migraine prevention based on their effectiveness in treating CRPS and suggested that migraine might be considered a form of “CRPS of the brain.” As outlined in the introduction, there is a higher incidence of CRPS and inflammatory diseases such as asthma and inflammatory bowel disorders in migraineurs, based on a shared pathophysiology of oxidative stress, FRS generation, and neurogenic inflammation 10–28 . Research has established that these processes, and in particular the generation of NO in the brain, plays a major role in migraine 17–25 .…”

“…However, over the past decade, research has shown that oxidative stress and the accumulation of oxygen and nitrogen free radical species (FRS) in the brain (in particular nitric oxide [NO]) also plays a major role in migraine pathophysiology 10–25 . FRS are chemically unstable and reactive oxygen or nitrogen moieties (eg, O 2 − , NO, H 2 O 2 ) produced during normal cell metabolism, which may accumulate in tissues, causing damage to lipid membranes, proteins, and DNA via peroxidation 26–28 …”

“…There is a higher than normal incidence of complex regional pain syndrome (CRPS), asthma, and inflammatory bowel disease in migraineurs, based on a shared pathophysiology of oxidative stress, FRS generation, and neurogenic inflammation 28–30 . There is also ample evidence of impaired oxidative‐antioxidant balance in patients with migraine, with increased FRS and reduced levels of antioxidants in their blood and CSF 11–13,31 . The free radical NO is a potent migraine trigger and is used to precipitate migraine attacks in experimental research 17–21 .…”

“…NO releases CGRP and substance P, activates platelets, and modulates the function of serotonin receptors, transient receptor potential cation channels (TRPV 1 ), potassium channels, and mitochondria. In the brain, these processes are linked to spreading cortical depression, cerebral vasodilation, and activation of the TCN, which are key processes in migraine generation 10–25,32 …”

Effectiveness of eye movement exercise and diaphragmatic breathing with jogging in reducing migraine symptoms: A preliminary, randomized comparison trial

“…For instance, eye–brain electrochemical transduction and retinal nerve fiber alterations, structural and functional abnormalities in the endothelial progenitor cells, interlinks between mitochondrial energy production, reactive oxygen species availability (e.g., nitric oxide—NO), and ion homeostasis (e.g., calcium influx) seem to play initiating roles in a brain with migraine (Ashina, 2020 ; DeBuc et al., 2020 ; Lee et al., 2008 ; Polak et al., 2003 ; Zhang et al., 2001 ). Therefore, regulation and availability of signaling biomolecules (e.g., NO, and brain‐derived neurotrophic factor—BDNF) and regulation of signaling pathways (e.g., cAMP‐response element‐binding protein—CREB) are essential during health and illness, including the symptoms of migraine attacks, as stressful insults to the brain (González‐Rodríguez et al., 2019 ; Khosravi et al., 2019 ).…”