A new era for migraine: The role of calcitonin gene-related peptide in the trigeminovascular system

There is a huge improvement in our understanding of migraine pathophysiology in the past decades. The activation of the trigeminovascular system has been proved to play a key role in migraine. Calcitonin gene-related peptide (CGRP) and CGRP receptors are widely distributed in the trigeminovascular system. The CGRP is expressed on the C-fibers, and the CGRP receptors are distributed on the A-delta fibers of the trigeminal ganglion and nerves. Further studies found elevated serum CGRP level during migraine attacks, and infusion of CGRP can trigger migraine-like attacks, provide more direct evidence of the link between CGRP and migraine attack. Based on these findings, several treatment options have been designed for migraine treatment, including CGRP receptor antagonists (gepants) and monoclonal antibodies targeting CGRP or CGRP receptors. The clinical trials show both gepants and monoclonal antibodies are effective for migraine treatment. In this section, we describe the roles of the trigeminovascular system in migraine, the discovery of CGRP, and the CGRP signaling pathway.