Views on migraine pathophysiology: Where does it start?

Migraine is a highly prevalent disorder (15.1% worldwide), afflicting up to 3 times more females in the middle ages than men. In most subjects, migraine attacks are sporadic; however, some individuals experience a gradual increase in frequency over time, and up to 1‐2% develop chronic migraine. Although migraine has been known for centuries, the mechanisms still largely remain unknown; two principal sites of origin are still in play: (i) intracranial vasculature and (ii) the origin in central regions such as hypothalamus, with both being suggested to activate the trigeminal vascular system. We share here our views on the pathophysiology of migraine and suggest that it starts in the CNS and involves the brainstem and finally the trigeminovascular system to complete the attacks. The recently developed monoclonal antibodies toward the neuropeptide calcitonin gene‐related peptide (CGRP) and its receptor provide key support for this line of events and are supported by preclinical experiments. The purpose of this review is to discuss our neuroscience perspective on migraine pathophysiology and putatively to serve as stimulus for future in‐depth studies.