Current perspectives on mitochondrial dysfunction in migraine

Abstract

Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the cerebral blood flow have for long been mechanisms underlying migraine. It is a neurovascular disorder with a unilateral manifestation of disturbing, throbbing and pulsating head pain. Migraine affects 2.6% and 21.7% of the general population and is the major cause of partial disability in the age group 15–49. Higher mutation rates, imbalance in concentration of physiologically relevant molecules and oxidative stress biomarkers have been the main themes of discussion in determining the role of mitochondrial disability in migraine. The correlation of migraine with other disorders like hemiplegic migraine; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes [MELAS]; tension‐type headache (TTH); cyclic vomiting syndrome (CVS), ischaemic stroke; and hypertension has helped in the assessment of the physiological and morphogenetic basis of migraine. Here, we have reviewed the different nuances of mitochondrial dysfunction and migraine. The different mtDNA polymorphisms that can affect the generation and transmission of nerve impulse has been highlighted and supported with research findings. In addition to this, the genetic basis of migraine pathogenesis as a consequence of mutations in nuclear DNA that can, in turn, affect the synthesis of defective mitochondrial proteins is discussed along with a brief overview of epigenetic profile. This review gives an overview of the pathophysiology of migraine and explores mitochondrial dysfunction as a potential underlying mechanism. Also, therapeutic supplements for managing migraine have been discussed at different junctures in this paper.

Multisite and multitimepoint proteomics reveal that patent foramen ovale closure improves migraine and epilepsy by reducing right‐to‐left shunt‐induced hypoxia

“…In this study, we also found that proteins related to mitochondrial organization changed after PFO closure, meanwhile the brain of PFO‐positive mice also showed enrichment of electron transfer and GTPase activity. These energy metabolic processes are probably associated with pathogenesis of migraine and epilepsy 74,75 . In subgroup analysis of epilepsy and migraine, we found proteins related to pyruvate metabolism increased after PFO closure in the peripheral blood of PWEs.…”

“…These energy metabolic processes are probably associated with pathogenesis of migraine and epilepsy. 74,75 In subgroup analysis of epilepsy and migraine, we found proteins related to pyruvate metabolism increased after PFO closure in the peripheral blood of PWEs. Previous studies have found that pyruvate metabolism disorder related to epilepsy not only provides energy for the brain, but also plays a brain protective role.…”

Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

“…There are similarities between the clinical features of migraine and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes) syndrome, which is primarily caused by a gene defect in mitochondrial DNA (mtDNA). A high prevalence of migraine was reported in individuals with certain mtDNA mutations 10,26 . Preclinical studies also demonstrated the activation of transient receptor potential ankyrin‐1 (TRPA1) in meningeal trigeminal nociceptors by reactive oxygen and nitrogen species (ROS/NOS), leading to neurogenic vasodilatation and CGRP release 21,27,28 …”

“…Furthermore, lactate levels were found to be high in migraine patients, indicating an impairment of mitochondrial metabolism in migraine 7,8 . Mitochondria regulates Ca 2+ homeostasis in excitable cells; however, mitochondrial dysfunction leads to abnormal Ca 2+ levels and excessive reactive oxygen species (ROS) production that may increase the possibility of migraine by inducing cortical spreading depression, a phenomenon underlying the migraine aura 9–11 . Moreover, disruptions in mitochondrial oxidative phosphorylation/brain oxidative energy metabolism during attack and attack‐free periods were displayed by phosphorus magnetic resonance spectroscopy studies 8,12 …”

“…7,8 Mitochondria regulates Ca 2+ homeostasis in excitable cells; however, mitochondrial dysfunction leads to abnormal Ca 2+ levels and excessive reactive oxygen species (ROS) production that may increase the possibility of migraine by inducing cortical spreading depression, a phenomenon underlying the migraine aura. [9][10][11] Moreover, disruptions in mitochondrial oxidative phosphorylation/brain oxidative energy metabolism during attack and attack-free periods were displayed by phosphorus magnetic resonance spectroscopy studies. 8,12 Emerging evidence indicates that there is a close relationship among oxidative stress, mitochondrial dysfunction, and inflammatory responses, 13 which may also be implicated in the pathogenesis of migraine.…”