Genes, proteases, cortical spreading depression and migraine: impact on pathophysiology and treatment.

Migraine headaches have a complex pathophysiology; both vascular and neuronal mechanisms have been proposed. One possible scenario begins with a series of destabilising events within the brain that trigger cortical spreading depression (CSD). CSD can cause both migraine aura and trigeminal activation which, in turn, promotes neuropeptide release and triggers peripheral and central mechanisms that promote headache and autonomic activation. Susceptibility to CSD and to migraine is, in part, genetically determined. The best evidence to date comes from certain subtypes of migraine with aura in which point mutations in genes controlling translocation of calcium, sodium and potassium have been implicated. This review briefly summarises recent migraine research that supports CSD as an upstream driver of the migraine attack as well as an activator of the trigemino-vascular system.