Voltage-gated calcium channels as potential therapeutic targets in migraine

Migraine is a complex and highly incapacitating neurological disorder that affects around 15% of the general population with greater incidence in women, often at the most productive age of life. Migraine physiopathology is still not fully understood, but it involves multiple mediators and events in the trigeminovascular system and in the central nervous system. The identification of CGRP as a key mediator in migraine physiopathology has led to the development of effective and highly selective anti-migraine therapies. However, this treatment is neither accessible nor effective for all migraine sufferers. Thus, a better understanding of migraine mechanisms and the identification of potential targets are still clearly warranted. Voltage-gated calcium channels (VGCCs) are widely distributed in the trigeminovascular system and there is accumulating evidence of their contribution to the mechanisms associated with headache pain. Several drugs used in migraine abortive or prophylactic treatment target VGCCs, which probably contributes to their analgesic effect. This review aims to summarize the current evidence of VGGC contribution to migraine physiopathology and to discuss how current pharmacological options for migraine treatment interfere with VGGC function. Perspectives CGRP represents a major target for migraine pathophysiology, but few studies investigated the relationship between CGRP and VGCCs. CGRP release is calcium channel dependent and VGGCs are key players in certain forms of familial migraines. Further studies are needed to determine whether VGCCs are suitable molecular targets for treating migraine.