Is the blood–brain barrier differentially affected by different variants of migraine?

This scientific commentary refers to ‘Ictal lack of binding to brain parenchyma suggests integrity of the blood–brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine’, by Schankin et al. (doi:10.1093/brain/aww096). In this issue of Brain , Schankin and co-workers study the permeability of the blood–brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks without aura, using PET with the novel radioligand 11C-dihydroergotamine (11C-DHE) (Schankin et al. , 2016). This radioligand is chemically identical to pharmacologically active DHE, a potent drug for the treatment of migraine headache. While 11C-DHE was seen to bind to structures that lack a blood–brain barrier such as the choroid plexus and pituitary gland, no binding was observed in the brain parenchyma either at rest or during attacks. Specifically, no binding occurred in the hippocampus, which shows the highest density of the highest affinity DHE receptors, and the raphe nuclei, a postulated brainstem site of action during migraine. The study thus suggests that the blood–brain barrier remains closed during attacks of migraine headache. This may guide the future development of anti-migraine drugs because it indicates that targets outside of the brain parenchyma are involved to such an extent in the generation and maintenance of migraine headache that pharmacological modulation of these …