Pathogenesis of migraine: the biobehavioural and hypoxia theories reconciled

The recent pathophysiological data obtained in migraine patients during and between attacks are reviewed in this article. They suggest that the headache in migraine is due to activation of the trigemino-vascular system. While this can be found in other headache disorders, the process leading ultimately to trigemino-vascular activation appears to characterize migraine. Between attacks, the migrainous brain has two functional abnormalities: a habituation defect in sensory processing, probably related to dysfunctioning transmitter (serotonin, noradrenaline) systems and a reduced mitochondrial energy reserve. Both abnormalities may be genetically determined and concur to favour biochemical shifts leading to the migraine attack as a primary protective mechanism of the brain. Such a model of migraine pathogenesis reconciles the biobehavioural and hypoxia theories and opens new therapeutic perspectives.