Migraine: a disorder of brain excitatory–inhibitory balance?

Migraine is a common disabling brain disorder whose key manifestations are recurrent attacks of unilateral headache and interictal hypersensitivity to sensory stimuli. Migraine arises from a primary brain dysfunction that leads to episodic activation and sensitization of the trigeminovascular pain pathway and as a consequence to headache. Major open issues concern the molecular and cellular mechanisms of the primary brain dysfunction(s) and of migraine pain. We review here our current understanding of these mechanisms, focusing on recent advances regarding migraine genetics, headache mechanisms, and the primary brain dysfunction(s) underlying migraine onset and susceptibility to cortical spreading depression, the neurophysiological correlate of migraine aura. We also discuss insights obtained from the functional analysis of familial hemiplegic migraine mouse models.