Recent progress in migraine pathophysiology: role of cortical spreading depression and magnetic resonance imaging

Abstract

Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among pain disorders in clinical conditions. We critically evaluate the scientific basis of various theories concerning migraine pathophysiology, and draw insights from brain imaging approaches that have unraveled the prevalence of cortical spreading depression (CSD) in migraine. The findings supporting the role of CSD as a physiological substrate in clinical pain are discussed. We also give an exhaustive overview of brain imaging approaches that have been employed to solve the genesis of migraine pain, and its possible links to the brainstem, the neocortex, genetic endophenotypes, and pathogenetic factors (such as dopaminergic hypersensitivity). Furthermore, a roadmap is proposed to provide a better understanding of pain pathophysiology in migraine, to enable the development of strategies using leads from brain imaging studies for the identification of early biomarkers, efficient prognosis, and treatment planning, which eventually may help in alleviating some of the devastating impact of pain morbidity in patients afflicted with migraine.

Patent Foramen Ovale With Atrial Septal Aneurysm Is Strongly Associated With Migraine With Aura: A Large Observational Study

“…Bhaskar et al conclude that cortical spreading depression is the physiological substrate of MA and probably also of MA− . Because the exact pathophysiology is not clear, the microthrombi hypothesis is still one of the many hypotheses for the cause of MA.…”

“…Bhaskar et al conclude that cortical spreading depression is the physiological substrate of MA and probably also of MAÀ. 23 Because the exact pathophysiology is not clear, the microthrombi hypothesis is still one of the many hypotheses for the cause of MA. Although no studies actually prove the microthrombi hypothesis, several case reports have been published showing benefit of warfarin in patients suffering MA.…”

Different mean thickness implicates involvement of the cortex in migraine

“…These techniques exhibit a high spatial resolution and are more sensitive to structural changes in the brain compared with other neuroimaging models such as computed tomography and positron emission tomography, thus presenting a more powerful capacity for the analysis of brain function. [5–7] Such studies have mainly focused on the resting state brain function, brain functional connectivity network, and brain structure of migraine patients. Functional MRI studies based on the resting state and task state have shown that the functions of some brain regions and the functional connectivity network of migraine patients are altered, and analyses of voxel-based morphometry have demonstrated that the volumes of some brain structures also exhibit differences.…”

Modulatory effect of synthetic kynurenic acid derivatives on the nitroglycerin-induced trigeminal activation and sensitization in rats

“…Another phenomenon partially explaining numerous symptoms of migraine is the theory linked to the cortical spreading depression (Bhaskar et al, 2013), which is an intense but slow continuous spread of excitation across the cerebral cortex followed by depression (Leao, 1944) and accompanied by slowly spreading cortical hypoperfusion as well (Olesen et al, 1981). This phenomenon is considered to be the physiological analogue of migraine aura, which is confirmed by studies using functional brain imaging (Hadjikhani et al, 2001).…”

“…Nevertheless, migraine is considered as a primarily genetically determined disease with a polygenic background (Pietrobon, 2007) and a large amount of candidate genes were implicated in migraine by genetic studies, but the mechanism, by which they actually participate in its pathophysiology, is still poorly understood (Bhaskar et al, 2013). A rare monogenic subtype of migraine is the familial hemiplegic migraine which causes attacks indistinguishable from the classical form and is associated with prominent aura symptoms (Pietrobon, 2007).…”