Abstract:
Migraine headache is highly debilitating, poorly understood, and difficult to treat. Mutations of human P/Q-type voltage-gated Ca2+ channels (VGCCs) associated with familial hemiplegic migraine type 1 (FHM-1) offer a gateway toward understanding the pathophysiology of FHM-1 as well as common migraine. Loss-of-function P/Q channel mutations cause a decrease of P/Q-type current in all subtypes of primary afferent neurons (PANs) in the pain pathways. Interestingly, only the PANs encoding headache become hyper-excitable as the result of P/Q mutations, consistent with the fact that FHM-1 patients show higher incidence of migraine headache but not other types of pain. Additional studies using a mouse model of headache suggest that P/Q and other VGCCs are involved in the onset of migraine in general population, not just FHM-1 patients. Ongoing experiments focus on dissecting the contribution of individual VGCC subtypes to migraine pathophysiology and their potential as targets for new migraine therapeutics.