Migraine is a common brain disorder, typically characterised by recurring, incapacitating attacks of 1-3 days of severe headache, autonomic dysfunction, and sometimes aura symptoms. The disease affects 15% of all European citizens including children, ranks among the WHO top 12 of most disabling and undertreated disorders, and is responsible for the highest socio-economic burden of any brain ailment in Europe.Migraine attacks typically strike bi-monthly, and in 25% of patients once a week or more. Many patients may progress to “chronic migraine” with near-daily headaches and high disability (chronification). There is desperate need of effective prophylactic treatments to prevent attacks and chronification. Current medications are only moderately effective and often poorly tolerated, mainly due to lack of understanding of how attacks are triggered and why their frequency may increase so dramatically. Overuse of painkillers and triptans, are recognised risk factors for chronification, as are comorbid depression, stress, and obesity. Central sensitisation of pain signalling pathways appears to be pivotal to the chronification proces.EUROHEADPAIN will use established and evolving human and translational animal models to: (a) identify pathways and biomarkers for the triggering and chronification of migraine attacks; (b) decipher the modulatory effects of (hypothalamic) brain circuitries on trigeminal processing, sensitisation, and chronification; (c) assess the effects and mode of action of migraine-provoking molecules; and (d) evaluate the efficacy and mode of action of neuromodulation (in collaboration with an SME) and second messenger-blocking drugs in the treatment of chronic migraine. We expect important spin-offs to the understanding of other chronic pain disorders. The pharmaceutical industry will be engaged once treatable targets have been identified to develop novel treatments to reduce the disability and socio-economic burden due to migraine.