Migraines: Causes and New Treatments

Sept. 17, 2002 -- Michael John Coleman remembers the first time he felt the excruciating pain of a migraine. He was 6 years old.

"I was looking out the window at school at a green field and my head really hurt. I was seeing spots and stars," recalls Coleman. "My teacher told me to put my head down and I saw a huge mass of clouds approaching. Then I felt nauseous."

Since that first onset, Coleman, who heads up MAGNUM, a Washington, D.C.-based migraine awareness group, has struggled with migraines his entire life, getting them at least twice a week. He says his migraines feel like "a gang of thugs" are smashing him in the head with baseball bats — over and over again. Like many migraine sufferers, his headaches are also preceded by an aura, a temporary state during which his vision is blurred and he sees spots.

The pain has been so brutal and unrelenting that he has had four surgeries to try and treat his condition. None have worked and instead made him feel worse.

But recently — only recently — he has become more hopeful about his condition. Better scientific understanding of migraine pain has led to drugs that can target specific causes, rather than offering a blanket-like numbing of head pain. Still, researchers admit, there's a lot left to learn.

"The problem with migraines is they seem to be a very heterogeneous disorder," explains Lawrence Newman, a neurologist at St. Luke's Roosevelt and Beth Israel Medical Center in New York City. "We're on the fringe of discovering its causes — we're close, but not yet close enough."

Fuzzy Outline

In the 17th century a physician named Sir Thomas Willis suggested that the intense headaches were caused by a rush of blood to the head. This increased blood flow led to swollen blood vessels that, in turn, placed uncomfortable pressure on the brain's nerve fibers.

That theory held up for centuries. But in the past decade, through the use of new noninvasive technology, such as MRI, PET and CT scans, researchers have learned that migraines may be caused by a series of complicated processes and that swollen blood vessels are likely a result, not a cause of the headaches.

Current research suggests that some migraines begin when nerve-rich arteries at the back of the brain spasm and lead to a reduction in neural activity throughout the brain. This reduction may be linked to the migraine aura, a condition experienced by about one in five people before a migraine.

Researchers at the University of Essen in Germany recently demonstrated that the process causing an aura is likely separate from those leading to the headache of a migraine.

In what the German researchers say may be a parallel process, a trigger in the brain stem causes the release of a cascade of chemicals. These chemicals aggravate the trigeminal nerve, the largest cranial nerve that branches along the jaw line, ear, face and into the sides and front of the brain. The agitated nerve then releases neurotransmittors, including the brain chemical serotonin, which come in contact with the brain's blood vessels and cause them to swell. The swelling is perceived as pain.

"The whole series of events is not entirely worked out. What causes the release of chemicals, for example? And where, exactly, does the process begin?" says Elizabeth Waterhouse, an associate professor of neurology at the Virginia Commonwealth University School of Medicine. "The general outline is there, but not the details."

Even having a "general outline" of migraine's causes, however, has boosted effective treatment of migraines.

Certainly times have improved from the 16th century when, according to MAGNUM, early physicians tried such approaches as drilling a hole through the skull to free "evil spirits," applying a hot iron to the site of pain or inserting a clove of garlic through an incision in the temple.

While treatment wasn't nearly as brutal in the 20th century, Coleman claims they weren't terribly effective either. In fact, he says it was often difficult to convince doctors that his pain was real.

"There was a common perception in this country that migraines were a psychological disorder," he says. "After spending two to three days in agony, with no sleep and projectile vomiting, I was often told by a physician that I wasn't really in any pain."

Until the early 1990s, a common treatment for migraines was narcotics — drugs that essentially put the whole brain to sleep to numb pain. Today medicines are available that can turn off the receptors of the trigeminal nerve and the brain's blood vessels.

A class of drugs, called triptans, emerged on the market in the early 1990s and have provided huge relief to migraine suffers (or migraineurs, as they're sometimes called). These drugs, which can now be taken in pill form, can kill a migraine within minutes since they directly hinder migraine chemistry.

Reducing Migraines — and Wrinkles

Through trial and error, more has also been learned about prevention. Among the most surprising finds was that Botox, a diluted version of the botulism toxin injected into the forehead to reduce wrinkling, can help prevent migraines.

"I may have been one of the biggest skeptics when this news came out," says Newman, who is a migraine sufferer as well as a specialist in the condition. "But I've been amazed at how well it works."

The first indications that Botox may prevent migraines first came from patients who had the procedure done for cosmetic reasons. They reported back to their doctors that their regular headaches had gone following the injections. Two years ago, a study led by Todd Troost, chairman of neurology at Wake Forest University, found that among 134 patients, Botox had a 92 percent success rate of decreasing migraines.

Other medications shown to ward off migraines include calcium-channel blockers that improve blood flow to the brain, antidepressants that regulate levels of the brain chemical serotonin and anti-seizure medicines.

A recent study even suggested that the friendly bacteria found in yogurt might help reduce migraines. This was based on the finding that some migraines may be linked to infection with a common bug and the bacteria in yogurt and other dairy products could fight them off.

The trick is finding which treatments work for which people. In the future, researchers hope to have a more precise tool for fighting migraines — gene therapy.

Nearly all people who suffer from migraines report they have family members with the same condition, suggesting a genetic factor is almost certainly at play. By knowing which genes make people vulnerable to migraines, it may be possible to manipulate these genes and prevent any onset of the headaches. The hunt is now on to find these genes.

Aarno Palotie, a professor of pathology and laboratory medicine at the University of California in Los Angeles, recently scouted out a particular band on a chromosome that, among 50 Finnish families, was consistently linked to a common form of migraine. Now his group is pursuing the actual genes at play on this chromosome.

Dutch researchers, meanwhile, have found a definitive genetic link to a more rare version of migraines called familial hemiplegic migraine.

"At some level, I suspect genes are at play in all migraine patients," says Palotie. "The tough part is understanding the interplay between the environment, the individual and genetic factors."

Avoiding Chocolate, Diet Sodas

The environment plays a clear role in triggering migraines, and through trial and error, migraineurs and researchers have pinpointed a few common triggers.

Alan Rapoport, director and founder of the New England Center for Headache in Stamford, Conn., and a colleague recently showed that 39 percent of migraine patients were sensitive to weather changes, such as increased humidity or temperature (although 90 percent believed they were).

Other work shows that 70 percent of women with migraines experience them during their menstrual cycles. Since women make up 75 percent of migraine sufferers, the female hormone estrogen is thought to play a certain role in triggering the condition.

Other kinds of triggers are more avoidable.

Chocolate, red wine, aged cheeses, cured meats, too much tea or coffee and overripe bananas have been shown to trigger migraines in many people. Coleman reports that aspartame — the sweetener found in many diet soft drinks — can give him a severe migraine within minutes. Other common migraine-inducing factors include too much or too little sleep, bright or flashing lights, strong perfumes, second hand smoke and air travel.

"The bottom line is if you can learn what's bothering you," says Coleman, "then you can avoid them and usually avoid a migraine."