The vascular theory of migraine—a great story wrecked by the facts

For much of the later part of the 20th century, a rather straightforward concept dominated thinking about migraine; first proposed in some part by Willis (1664) and best articulated by Wolff (1948), the theory explained the pain of migraine to be due to dilation of cranial vessels. By the latter part of the 19th century, neuronal theories had also been well articulated (Liveing, 1873) and, indeed, Gowers (1888) seemed happy with that concept. It is remarkable that three key approaches revived the vascular theory in the mid- to late-20th century; and the same three key areas—human experimental studies, observations on vascular change and therapeutics—have, some 120 years later, put migraine back into the brain, and thus firmly into the domain of neurology.This issue of Brain describes a study with exactly the type of result that lead Wolff to think of migraine as vascular; yet, taken in context, it provides evidence that leads to precisely the opposite conclusion. Henrik and colleagues (2008) from the Copenhagen group demonstrate in their new study pituitary adenylate cyclase activating …