Migraine and the trigeminovascular system—40 years and counting

The causes of migraine headaches puzzled researchers throughout much of the 20th century. In 1979, a significant hypothesis emerged, highlighting the trigeminal nerve's role. This idea transformed the migraine research landscape. It emphasized neuropeptides and their release from trigeminal nerve endings. This understanding shed light on migraine mechanisms and how anti-migraine drugs work. Researchers discovered that blocking neuropeptide release could alleviate migraines. Meningeal inflammatory stimuli and intense brain activity also activate trigeminal afferents. Notably, antisera targeting calcitonin gene-related peptide (CGRP) and substance P neutralized their effects. These findings led to effective treatments using monoclonal antibodies against CGRP and its receptor. Today, the trigeminovascular system is recognized as crucial in understanding migraines. This progress provides a roadmap for developing future migraine therapies. Overall, the past four decades have significantly advanced our understanding of migraine. Clinical relevance: This research highlights the importance of the trigeminovascular system in migraine treatment.