Current concepts of migraine pathogenesis
Abstract
Migraine is a neurovascular reaction to sudden changes in the internal or external environment. Each individual has a hereditary "migrainous threshold," with the degree of susceptibility depending on the balance between excitation and inhibition at various levels of the nervous system. The mechanism of migraine has been presented as an unstable trigeminovascular reflex with a segmental defect in the pain control pathway. This defect permits excessive discharge of part of the spinal nucleus of the trigeminal nerve and its thalamic connections in response to excessive afferent input or corticobulbar drive. The end result is the interaction of brain stem and cranial blood vessels, with the afferent impulses from the latter creating the throbbing (pulsating) character of the headache. Diffuse projections from the locus ceruleus to the cerebral cortex could initiate cortical oligemia and possibly spreading depression. Activity in this system could account for the migrainous aura that may occur quite independently of the headache. The headache phase may be interrupted by therapy aimed at either the central or peripheral end of the trigeminovascular afferent pathway. Strong evidence suggests that serotonin (5-hydroxytryptamine, 5-HT) plays an important part in the genesis of migraine. Whether 5-HT is effective in central pain control pathways, the serotonergic projection to the cerebral cortex, its direct action on the cranial blood vessels, or its action at all three sites remains…
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