16 Mechanisms of Migraine and Its Treatment

Migraine is characterized by recurrent unilateral headaches, accompanied by nausea, vomiting, photophobia, and/or phonophobia, and in some cases facial symptoms. Current theories suggest that the initiation of a migraine attack involves a primary CNS event, putatively involving mutations in ion channels that render the individuals more sensitive to environmental factors, resulting in a wave of cortical spreading depression when the attack is initiated. Early positron emission tomography (PET) suggested the involvement of a migraine active region in the brainstem. In migraine attacks, data suggest that the pain is associated with the activation of the trigeminal nerve and the release of calcitonin gene-related peptide (CGRP) from the trigeminovascular system. Administration of triptans (5-HT1B/1D receptor agonists) causes the headache to subside and the levels of CGRP to normalize. Administration of CGRP receptor antagonists aborts the headache by specifically blocking the CGRP receptors located within the trigeminovascular system. Modern acute migraine therapy involves modulation of both CGRP and 5-HT1B/1D receptors.