Neurogenic Inflammation in Migraine: New Horizons in Migraine Treatment

Migraine is a common primary headache disorder and ranked as the second most disabling disorder worldwide. Although various studies performed to understand the pathogenesis of migraine disorder, the exact pathogenic mechanism is still unclear. Recently, considerableimprovement in molecular biology and pharmacology illustrated that neurogenic inflammation is likely to be a mechanism involved in the migraine pathophysiology. This neurogenic inflammation is described by the release of sensory neuropeptides such as Calcitonin gene-relatedpeptide (CGRP) from activated trigeminal neurons, leading to vasodilation, degranulation of mast cells, and sensory transmission. Further research advancements considering the role of neurogenic inflammation in migraine, proposed that targeting CGRP pathway byblocking the CGRP ligand or CGRP receptor might have putative role in the treatment of migraine. Targeting the CGRP pathway led to development of novel therapeutic anti-migraine drugs: CGRP receptor antagonists (Gepants) for acute treatment of migraine and antiCGRP monoclonal antibodies as promising preventive treatments. I will review the CGRP peptide and its role in migraine pathophysiology in order to better understand the mechanism through which, emerging novel therapies targeting the CGRP pathway act. I will also summarize the main results of phase II/III randomized clinical trials on these drugs.