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Mechanisms and Treatment of Migraine and its Chronification

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Biomarkers promise relief for migraine sufferers

Migraine often involves incapacitating attacks of severe headache and autonomic nervous system dysfunction lasting up to three days. The disease affects 15 % of all European citizens and as such, is responsible for the highest socio-economic burden of any brain ailment in the continent.

Fundamental Research
Health

The EU-funded EUROHEADPAIN project aimed to identify and investigate predictive and pathophysiological biomarkers for the susceptibility and initiation of migraine attacks. Also investigated was development of chronic migraine characterised by nearly daily episodes. The multidisciplinary EUROHEADPAIN consortium used data from many thousands of well phenotyped and genotyped migraineurs. In addition, clinical, pharmacological, genetic, biochemical, neurophysiological and (functional) neuroimaging information is available. Using functional magnetic resonance imaging outside an attack and, when possible, through the transition until an attack occurred, the team studied patients with episodic or chronic migraine. Brain changes were recorded giving insight into where attacks started and how they progressed. Whenever possible, in the same patients, researchers recorded biochemical changes in plasma and CSF and neurophysiological changes. By integrating these data, a first analysis was performed to obtain (interictal) biomarkers for diagnosis of and susceptibility to migraine and chronification. For information on initiation pathways and to obtain predictive and initiation biomarkers, neurophysiological and neuroimaging profiling characterised the transition from pre-ictal to ictal phases. Translational studies in transgenic mice carrying migraine monogenic mutations supplied detailed mechanistic insight on brain changes relevant to migraine pathophysiology. Complementary read-outs from cell culture systems and animal studies made it possible to dissect peripheral and central (hypothalamic) mechanisms for the generation and modulation of migraine pain. This information was fed by genetic profiles with many identified genetic factors and associated molecular pathways. Genetic findings highlight risk factors for episodic and chronic migraine and can – to a certain extent - predict or assess treatment response. To develop novel treatments, the team devised provocation target tests and deciphered triggering pathways by provoking attacks in healthy subjects and I patients using pharmacologically different molecules. The EUROHEADPAIN project has also devised improved options for non-invasive neuromodulation of chronic and episodic migraine in close collaboration with an SME. Moreover, research results have advanced the understanding of how neuromodulation works using neurophysiological and neuroimaging tools. Various drugs for the treatment of chronic migraine are expected.

Keywords

Biomarkers, migraine, EUROHEADPAIN, chronic, drugs

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