CURRENT CONCEPTS OF MIGRAINE PATHOGENESIS

Migraine is a neurovascular reaction to sudden changes in the internal or external environment. Each individual has a hereditary ''migrainou s threshold,'' with the degree of susceptibility depending on the bala nce between excitation and inhibition at various levels of the nervous system. The mechanism of migraine has been presented as an unstable t rigeminovascular reflex with a segmental defect in the pain control pa thway. This defect permits excessive discharge of part of the spinal n ucleus of the trigeminal nerve and its thalamic connections in respons e to excessive afferent input or corticobulbar drive. The end result i s the interaction of brain stem and cranial blood vessels, with the af ferent impulses from the latter creating the throbbing (pulsating) cha racter of the headache. Diffuse projections from the locus ceruleus to the cerebral cortex could initiate cortical oligemia and possibly spr eading depression. Activity in this system could account for the migra inous aura that may occur quite independently of the headache. The hea dache phase may be interrupted by therapy aimed at either the central or peripheral end of the trigeminovascular afferent pathway. Strong ev idence suggests that serotonin (5-hydroxytryptamine, 5-HT) plays an im portant part in the genesis of migraine. Whether 5-HT is effective in central pain control pathways, the serotonergic projection to the cere bral cortex, its direct action on the cranial blood vessels, or its ac tion at all three sites remains uncertain. It seems probable that the 5-HT agonists act to terminate migraine through the cerebral and extra cranial circulations, whereas medications used for prophylaxis may act centrally.