A critical review of the neurovascular nature of migraine and the main mechanisms of action of prophylactic antimigraine medications.

In the last three years, migraine prophylaxis has evolved from nonspecific to specific antimigraine treatments. Overall, nonspecific treatments  mainly involve neural actions, whereas specific pharmacotherapy (represented by CGRP receptor antagonists and CGRPergic monoclonal antibodies) is predominantly mediated by neurovascular mechanisms that may include, among others: (i) reduction in the cortical spreading depression (CSD)-associated events; (ii) inhibition of pain sensitization; (iii) blockade of neurogenic inflammation; and/or (iv) increase in cranial vascular tone. Accordingly, the novel antimigraine prophylaxis promises to be more effective, devoid of significant adverse effects (unlike nonspecific treatments), and more beneficial for the quality of life of migraineurs.