Migraine headaches are marked by repeated, paroxysmal attacks of moderate-to-severe throbbing, one-sided headaches which (without treatment) last 4 to 72 hours and are usually associated with symptoms of nausea and vomiting. Migraine headaches are typically exacerbated by motion, bright lights and loud noises. Migraines may be associated with focal neurological symptoms referred to as “aura” which are typically visual, but may be sensory or motor. Migraine headaches are common, affecting at least 18% of women and 6.5% of men in the United States. The pattern of paroxysmal headaches typically arises in adolescence or young adulthood and may be life-long. The headaches often interfere with daily activities and can be incapacitating, result in major time lost from work and precipitate multiple physician and emergency room visits. Patients with migraine may also be at increased risk for other vascular complications such as stroke and eclampsia.
The cause of migraine headaches is not fully understood, but appears to be related to arteriolar vasodilation and inflammation of the trigeminal nerve endings, perhaps caused by local release of vasoactive peptides. Serotonin activity appears to lessen the pain and symptoms of migraine and serotonin receptor agonists have been developed that have activity against acute migraine. However, the most convincing candidate mediator of migraines is the calcitonin gene related protein (CGRP), a neuropeptide with potent vasodilator and pain-signaling activities. CGRP is found throughout the central and peripheral nervous systems but is particularly active in trigeminal ganglia. Circulating levels of CGRP are elevated in patients with migraines, and the efficacy of migraine therapies such as serotonin receptor agonists and ergot alkaloids is associated with lowering of circulating CGRP levels. Antagonists of CGRP have become a focus of migraine headache prevention and therapy.
Therapy of migraine headache usually combines preventive treatments with early intervention for acute attacks. Early treatment approaches to migraine have included a number of different classes of medications, including analgesics such as aspirin, nonsteroidal antiinflammatory agents and opiates, barbiturates, antiemetics, ergot alkaloids, two types of serotonin receptor agonists (triptans and ditans), and oral, small molecule CGRP antagonists.