Migraine: New molecular mechanisms

Migraine is an episodic headache disorder affecting more than 10% of the general population. Migraine arises from a primary brain dysfunction that leads to activation and sensitization of the trigeminovascular system. A major incompletely understood issue in the neurobiology of migraine concerns the molecular and cellular mechanisms that underlie the primary brain dysfunction and lead to activation and sensitization of the trigeminovascular system, thus generating and maintaining migraine pain. Here the author reviews recent discoveries that have advanced our understanding of these mechanisms toward a unifying pathophysiological hypothesis, in which cortical spreading depression (CSD), the phenomenon underlying migraine aura, assumes a key role. In particular, the author discusses the main recent findings in the genetics and neurobiology of familial hemiplegic migraine and the insights they provide into the molecular and cellular mechanisms that may lead to the increased susceptibility of CSD in migraineurs.