Margit was only 19 when the horrific headaches began. In the middle of training to become a physical therapist, she found that the right side of her head began pounding, as if her skull were about to explode. For a while that first time, she muddled through the day, doing her best to ignore the pain, made worse by the blinding artificial light and stress of the clinic.

But eventually she went home, pulled down the blinds and fell asleep on the couch. When she woke up—15 hours later—she felt weak, but better. Perhaps it was just a fluke.

The same thing happened a month later, though, and the episodes recurred every few weeks for the next two years. Rather than seeing a doctor, Margit tried to hide her pain. She did not want co-workers thinking she was a whiner. She valued her job, which was on the surgical ward of a large city hospital.

Then one day, on her way to the treatment room, yellow zigzags flashed before her eyes, distorting her vision. "I couldn't see straight!" the now 34-year-old recalls. Frightened, she told an older co-worker. "It's just a migraine," the co-worker told her.

About 6 percent of men, 18 percent of women and 4 percent of children get migraines—28 million people in the U.S. alone. Their intense, throbbing pain, which is usually concentrated on one side of the head and often accompanied by nausea and vomiting, typically lasts for hours and can put a person out of commission for up to three days. Movement, light and noise usually intensify the misery of a migraine.

In some patients, migraines announce themselves with an "aura," made up of strange visual sensations such as the appearance of zigzag lines, blind spots or shimmering lights. Migraines may also be preceded by sudden mood changes, speech disturbances and even transient paralysis, according to Guy Arnold, a headache specialist at Charit Medical School in Berlin.

Migraines were long thought to have no serious medical consequences besides the pain, but recent data suggest otherwise. Women who experience auras before a migraine have double the risk of stroke, heart attack and dying from cardiovascular disease, according to a study in the July 2006 Journal of the American Medical Association by Tobias Kurth and his colleagues at Brigham and Women's Hospital in Boston. In recent years, researchers also have gained a new, better understanding of the biological origins of migraines. This has led to an expanded arsenal of migraine treatments that provide new hope to people who experience these extraordinary headaches.

Hitting a Nerve
Ancient artistic renderings suggest that the Egyptians suffered from migraines more than 3,000 years ago. Greek physician and philosopher Galen (who lived circa A.D. 129216) claimed that an excess of "black bile" caused the symptoms. Because of the asymmetry of the pain, he called these headaches hemicrania (from the Greek hemi, meaning "half," and kranion, or "skull"). The word gradually morphed into hemigrania, emigranea, migranea--and finally, migraine.

Scientists thought for years that migraines were caused by the contraction and expansion of blood vessels in the head. Now many believe that nerve tissue is the primary culprit. Studies in the 1990s using the imaging technique positron-emission tomography (PET) showed that the attacks seem to arise when nerves deep within the brain stem, the lower part of the brain that abuts the spinal cord, become overstimulated.

Numerous nerves sprout from the brain stem, including fibers of the massive trigeminal nerve, which supplies sensory information to many parts of the face and head and also controls some facial muscles. When the endings of the trigeminal nerve become overwrought, because of genetic or environmental factors, or both, they release large amounts of chemicals called neuropeptides, according to Peter Storch, who heads the headache clinic at the University of Jena in Germany. This release spawns inflammation in nearby blood vessels and thereby excites pain receptors of the trigeminal nerve, whose signals reach the brain stem, Storch says. At the brain stem, pain-processing centers can become sensitized or overloaded and start firing spontaneously, producing the pain of migraine.

This recent understanding of migraine has led to new treatments. For example, drugs called triptans inhibit the release of the neuropeptides now considered central to the physiology of migraines. Triptans work by docking to specific receptor molecules on the trigeminal nerve--the same receptors that ordinarily bind to the natural nerve messenger serotonin. The attachment of either substance to these receptors stops the nerve from spewing out neuropeptides and thereby interrupts the cascade of pain. Thus, many patients try to stop a nascent migraine in its tracks or reduce its severity with medications containing the active ingredient sumatriptan, naratriptan, rizatriptan or the like. These triptan drugs must be taken right away to have any effect, however.

An Ounce of Prevention...
Better yet, of course, would be to prevent migraines from occurring in the first place. Many patients can identify environmental triggers. For many migraine sufferers, including Margit, stress plays an important role. "The more stress I'm under, the more frequently I get migraines," Margit says.

To relieve stress, doctors often recommend exercises that require endurance. Margit sometimes takes a long jog in the woods, for example. Migraine researcher Storch also suggests a technique called progressive muscle relaxation (PMR) for stress relief. In PMR, a person deliberately tenses--and then relaxes--one muscle group at a time in a specific order. In other cases, though, a person simply has to slow down. "When I recognize that I'm piling on too much stress, I'll downshift for a while," Margit says. Her strategy helps her.

In other people, erratic sleep patterns set off migraines. For these sufferers, getting up at the same time every day--that is, not sleeping in on weekends--can often solve the problem. Too little sleep can spark a migraine, too, so going to bed on time can also be important. And for some, migraine prevention means avoiding something--for instance, cigarette smoke or certain foods, such as red wine or chocolate.

In women, up to 60 percent of migraines are set off by the drop in estrogen that precedes the menstrual cycle. Women can often prevent or reduce the severity of these migraines by taking estrogen in patch or pill form beginning two or three days before their menstrual period, which smooths out the natural drop in estrogen. Because the menstrual cycle is often predictable, treatments such as triptans that are usually taken during a migraine can head it off instead, if used within a day or two before a migraine is expected to begin.

If migraines occur more than three times a month or last longer than 72 hours, doctors recommend that a patient take medication at regular intervals to prevent the attacks. Most prophylactic drugs for migraines were developed to treat conditions from epilepsy to depression. Such drugs can often reduce the number of attacks by half or more and lessen the severity of the migraines that still occur.

Researchers have become increasingly interested in the past few years in using antiseizure drugs such as topiramate (Topamax) and valproic acid (Depakote) to prevent migraine attacks. Such drugs dampen the excitability of nerve cells and thereby reduce the sensitivity of the brain to external stimuli, Arnold says.

The U.S. Food and Drug Administration approved topiramate for migraine prevention just two years ago, after Stephen D. Silberstein of Thomas Jefferson University Hospital in Philadelphia and his colleagues reported its effectiveness in a large-scale clinical trial. The researchers found that doses of topiramate of 100 milligrams or more shrank migraine frequency by almost half--from more than five headaches per month to just over three in the roughly 370 patients who took topiramate for the six-month study period; in contrast, a placebo pill produced a much smaller change. In 2006 neurologist Alan M. Rapoport and his team from the New England Center for Headache in Stamford, Conn., extended these findings, showing in a study of more than 550 patients that topiramate's benefits lasted for up to 14 months. In both studies, the drug did sometimes cause patients to feel fatigue, nausea, and numbness in one or more body parts. Some also lost a lot of weight.

Yet migraine researchers such as Storch consider such problems more palatable than the excessive weight gain that comes with beta blockers, which slow certain nerve impulses, or calcium antagonists, which ease blood flow; both are high blood pressure medications that are also used to prevent migraines. But some patients gain so much weight on these drugs that they stop taking them, Storch says.

Pressure Points
For patients who either cannot take or prefer to avoid drugs, migraines may succumb to a variety of alternative remedies. Klaus Linde of the Center for Complementary Medicine Research at the Technical University of Munich and his colleagues tested acupuncture against these throbbing demons. They assigned more than 300 migraine patients to either one of two eight-week regimens--12 sessions of acupuncture or 12 sessions of sham acupuncture, in which the needles are not placed in the classical acupuncture points--or to a spot on the waiting list. They found that both needle treatments made a big difference: about half the people in those groups found that it cut their "headache days" in half. In contrast, only 15 percent of people on the waiting list saw similar improvement.

In a follow-up study of nearly 1,000 patients, researchers from the University of Duisberg-Essen in Germany reported in 2006 that both acupuncture and fake acupuncture are just as good at preventing migraines as beta blockers, calcium channel blockers and antiepileptic drugs are. Researchers surmise that the needle therapy's success comes in part from its ability to relax the patient and provide him or her with a lot of personal attention.

Other nondrug techniques for taming migraines include biofeedback, in which patients learn to control body functions that are normally automatic, such as breathing and heartbeat, often with the help of a feedback machine and a therapist, and a lesser known relaxation method called autogenic training. In the latter approach, patients practice specific exercises that make the body feel warm, heavy and relaxed. These techniques often allow patients to target the tension in the blood vessels, which can ameliorate their headaches. Some practiced patients can even use them to get immediate relief from pain.

Margit heads off her migraines in less formal ways. She listens far more closely to her body's signals than she did before her headaches began, and she shuns activities at work or at home that might bring on excess stress. When such efforts fail and a migraine looms, she also knows what to do: she heads for darkness and quiet. Then she sleeps.