CGRP: New Focus in Migraine

Migraine is a neurological disorder characterized by recurrent attacks of headache usually accompanied by symptoms such as nausea, vomiting, photophobia and phonophobia. According to the Global Burden of Disease Study 2019 estimates, it affects more than 1.12 billion people worldwide and is a major cause of disability worldwide. Although migraine has been recognized for centuries, its pathophysiology has not been fully understood yet. Several theories have been proposed so far, the most recent being the neurovascular theory. Supported by the developments in neuroradiology and immunohistochemistry, the theory emphasizes the essential role of the trigeminovascular (TGV) system in migraine pathophysiology. It is obvious that the TGV system, regulating the cranial blood flow and nociceptive transmission, contributes to initiation and progression of serial complex events associated with migraine. The identification of vasoactive neuropeptides which had a role in migraine pathophysiology also created an opportunity for development of new treatment strategies in migraine. Calcitonin gene related peptide (CGRP) is one of the neurotransmitters that has attracted most attention since it is abundantly found in the TGV system and plays a significant role in different processes of migraine including vasodilation, neurogenic inflammation, peripheral and central sensitization. It became the focus of research in the last few decades and extensively investigated. Both small molecules antagonizing CGRP receptor and monoclonal antibodies targeting either CGRP or its receptor have been developed and used in migraine treatment. This article overviews the role of the TGV system in migraine pathophysiology and treatment with a specific focus on CGRP.