Targeting neuronal hyperexcitability for antimigraine drug development

Migraine is among the most prevalent neurological disorders worldwide, afflicting up to 16% of the population. Because it mostly affects patients between the most productive ages of 25 and 50 years, migraine costs employers more than US$13 billion per year in reduced productivity and missed days. It is therefore important to prevent and treat migraine attacks. Triptans were introduced in the early 1990s and effectively alleviate symptoms in most patients. Their success was based on the existence of the operational hypothesis implicating the trigemino-vascular system. Prophylactic medications have been available since beta-blockers, followed by agents belonging to other therapeutic classes. Most of them were found serendipitously to be effective. However, progress in the development of preventative agents has been hampered by the lack of animal models mimicking the early events of migraine pathophysiology. This review will examine how a recent theory on the origin of migraine attacks is likely to lead to the development of new animal models.