Headache: classification, mechanism and principles of therapy, with particular reference to migraine.

The sensation of pain derived from intracranial and extracranial blood vessels is conveyed to the central nervous system chiefly by the trigeminal nerve, with first order neurones terminating in the nucleus caudalis of the spinal trigeminal tract and an area lateral to the dorsal horn of the spinal cord at the second cervical segment. The evoked discharge of second order neurons can be suppressed by activation of the endogenous pain control system or, in about one third of cases, by the local application of ergot derivatives or the serotonin (5HT1) agonist sumatriptan (GR43175). Stimulation of brainstem structures such as locus ceruleus, raphe nuclei and the trigeminal system induce changes in the cerebral and extracranial circulations of the experimental animal that mimic those of migraine with aura (classical migraine). Clinical and laboratory observations have led to a neural hypothesis for migraine in which changes in hypothalamic function (an 'internal clock') and reactions to stress or excessive afferent stimuli are thought to initiate brainstem activity, causing secondary vascular changes and release of inhibition of the trigeminal pain pathways to cause headache. Painful distension of cranial blood vessels may contribute the throbbing component to migraine headache. Migraine is associated with a lowered level of platelet serotonin that is thought to reflect monoamine depletion in brainstem nuclei. Migraine headache can be precipitated by reserpine, which releases serotonin from body stores, and relieved by the intravenous infusion of serotonin. The new 5HT1 agonist sumatriptan promises to have the beneficial effects of serotonin without the side-effects that limited its clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)