Refractory migraine and chronic migraine: pathophysiological mechanisms.

Migraine is a complex disorder of the brain whose mechanisms are only now being unravelled. It is common, disabling, and economically costly. Brain imaging has suggested a role for the brainstem. While the disorder is almost certainly inherited, the degree to which this contributes to a treatment refractory state is not clear. Indeed, no specific structural or pharmacological explanation can be seen from the data as they have been generated. It is clear that patients with more frequent headache are very likely to go on to even more frequent headache, but again these data are complex. A challenge going forward is to establish the biology of these very challenging patients who undoubtedly have substantial disability.