Revisiting Migraine: The Evolving Pathophysiology and the Expanding Management Armamentarium

Migraine affects about one billion people worldwide yearly and is one of the most common neurologic illnesses, with a high prevalence and morbidity, particularly among young adults and females. Migraine is associated with many comorbidities, including stress, sleep difficulties, and suicidal ideation. Migraine, despite its widespread occurrence, is underdiagnosed and undertreated. Because of the complicated and primarily unknown mechanisms of migraine formation, several social and biological risk factors, such as hormone imbalances, genetic and epigenetic impacts, and cardiovascular, neurological, and autoimmune illnesses, have been proposed. Through the mid-20th century diversion of the now-defunct vascular theory, the pathophysiology of migraine has developed from a historical study of the "humours" to a distinct entity as a neurological disorder. The range of therapeutic targets has broadened significantly, increasing the number of specialized clinical trials. Understanding the biology of migraine through careful research has resulted in the identification of major therapeutic classes: (i) triptans, serotonin 5-HT1B/1D receptor agonists, (ii) gepants, calcitonin gene-related peptide (CGRP) receptor antagonists, (iii) ditans, 5-HT1F receptor agonists, (iv) CGRP monoclonal antibodies, and (v) glurants, mGlu5 modulators, with further targets being explored. This review provides a comprehensive overview of the most recent literature on epidemiology and risk factors and exposes knowledge gaps.