High-maintenance, hypersensitive, demanding, and overly excitable — the “migraine brain” insists that everything in its environment remain stable and even-keeled. Carolyn Bernstein, M.D., and Elaine McArdle, authors of The Migraine Brain: Your Breakthrough Guide to Fewer Headaches, Better Health, explain what it means to have a migraine brain.
Let’s say you drink a glass of red wine in a smoky bar after a really stressful day at work, and each of those stimuli happens to be a migraine trigger for you. Your Migraine Brain reacts, sending chemical and pain signals throughout your brain and body. You end up with a pounding headache and huddled over the toilet in the women’s room. What, exactly, is happening in your body?
For many years, migraine was was believed to be a problem with the vascular system (your blood vessels and the circulation of blood to body organs). Many doctors thought that migraines were caused by vasodilation—blood vessels in the brain expanding and pressing on painsensitive structures. But this theory wasn’t perfect. It didn’t explain many of the characteristics of migraine attacks, such as nausea and aura.
In recent years, our understanding of migraine has progressed a great deal. We now know it is a complex neurological disease that involves much more than the vascular system. The vasodilation theory was probably backwards: migraines aren’t caused by blood vessels expanding; rather, blood vessels are thought to expand as a result of a migraine attack.
The new science of migraine recognizes that migraine disease involves many aspects of your physiology, including your central nervous system, neurotransmitters and other chemicals in your brain, electrical impulses, your inflammatory response, a nerve in your face and head called the trigeminal nerve, and other systems. The latest research points to “cortical spreading depression” as the physical reaction that begins a migraine attack. It isn’t a depression at all but in fact is just the opposite, a superexcitability of the brain. Cortical spreading depression is a dramatic wave of electrical “excitation” that spreads across the surface of the brain, also called the cerebral cortex, when something antagonizes or upsets it. The cerebral cortex is responsible for many complex functions in the body including processing sensory information, executing voluntary movement, and handling the functions of language, thought, perception, and memory, which is why these functions can be affected during a migraine attack. For example, the spreading excitatory wave can be the cause of visual aura or tingling up your arm, while the cortical “depression” that follows can cause blind spots or numbness.
Cortical spreading depression was first described in 1943 by a Brazilian scientist named Aristide Leao, who, in a series of experiments, opened the skulls of rabbits and pricked their brains with a pin. When he did so, he observed actual waves of electrical reaction emanating outward from the site of the pinprick. But a pinprick is not the only stimulus that evokes cortical spreading depression. Every brain, if antagonized (such as by a medication, chemical imbalance, or some other stressor), can be susceptible to cortical spreading depression. It seems that people with migraine disease have a low threshold for cortical spreading depression (CSD), and it doesn’t take a very strong stimulus to set off CSD in the Migraine Brain. This susceptibility to CSD appears to be inherited, but we also suspect it can be induced through extreme circumstances.
Researchers have found that CSD seems to explain many if not all aspects of migraine. At first, they believed CSD was related only to the aura phase of migraine, but we now believe it may well be the underlying basis for most things migraineurs experience during an attack.
The CSD model of migraine also explains why certain drugs— some of which were developed for other conditions such as epilepsy or depression—work to prevent migraine. These drugs aren’t similar to each other in their chemical properties, but they do share a common feature: they appear to raise the threshold for aggrivating CSD. In other words, these drugs may make your brain less excitable. In an experiment at Massachusetts General Hospital, researchers found that daily doses of selected migraine drugs reduced the frequency of CSD by 40 to 80 percent.
Here’s how we now believe migraine works: A migraineur’s central nervous system is overly sensitive to certain stimuli. When it encounters something it doesn’t like—a change in weather, let’s say, or fluctuations in estrogen levels—it sends a “red alert” to your overly excitable Migraine Brain, which reacts by setting off cortical spreading depression. In CSD, a wave of electrical excitement moves rapidly across your brain. (Don’t get worried about the electrical activity here—it doesn’t mean you’re in danger of electrocution.) During CSD, nerve cells in your brain become depolarized initially, then hyperpolarized, causing “depression.” In short, cell membranes, the outer protective layer of each cell, become unstable, allowing changes in the usual chemical balance. This instability spreads to other nearby cells in a chain reaction.
This wave of excitement does a number of things, including igniting the trigeminal nerve, a sensory nerve on either side of your face and head that supplies sensation and pain to your face, head, and the nerve roots at the top of your spine that supply the scalp. The trigeminal nerve then releases neuropeptides, small proteins that cause inflammation and dilate blood vessels in your head and around your brain.
According to the research, migraine involves what’s called an ionopathy or abnormality of the flow of chemicals in your brain across cell membranes, including serotonin, dopamine, and norepinephrine. Serotonin (also called 5-HT), a neurotransmitter you’ve probably heard of, is a critically important chemical messenger best known for its role in depression and other mental health disorders. Serotonin is also part of the pain-regulation process, and migraineurs have certain abnormalities in their serotonin function. During a migraine, serotonin levels rise and then fall, affecting nerve cells in the brain and aggravating CSD.
In 1992, sumatriptan, which goes by the brand name Imitrex, was introduced to the market, the first of a kind of medicine called triptans designed specifically to address the chemical chain reaction of migraine. There are now six other triptans on the market. The key thing to know about triptans is that they are not painkillers, per se. Before triptans came on the market, the most commonly prescribed migraine treatments were painkillers, which didn’t do much beyond mask the pain—not always very well—and which had serious possible side effects including addiction and rebound headaches. Triptans are an entirely different kind of migraine drug, in a class of drugs called serotonin agonists, which work by mimicking serotonin and attaching to specific serotonin receptors in the brain, allowing some cells to use serotonin more effectively. Triptans also stop the release of neuropeptides, the small proteins that cause inflammation, dilate the blood vessels, and set off pain.
Because triptans interrupt the biochemical mechanism of a migraine, they can be effective in treating the entire menu of migraine symptoms including nausea and vomiting. And they can be incredibly effective. At least 80 percent of migraineurs get relief when they use triptans. Doctors and migraineurs with experience in triptans, including me, view them as a miracle drug. For most people, they are safe to use with few or no side effects.
ABOUT THE AUTHOR
Carolyn Bernstein, M.D., co-author of The Migraine Brain (Copyright © 2008 by Carolyn Bernstein, M.D. and Elaine McArdle), is an assistant professor of neurology at Harvard Medical School and a staff neurologist at Cambridge Health Alliance in Cambridge, Massachusetts. A board-certified neurologist, Dr. Bernstein belongs to the American Academy of Neurology. In 2006, Dr. Bernstein won the Harvard Medical School Faculty Prize for Teaching Excellence, and in 2007, she was the recipient of the Leonard Tow Award for Humanism in Medicine given by Harvard Medical School and the Arnold Gold Foundation. In 2007, she also won the National Headache Foundation’s Headache Healthcare Provider of the Year. In 2006, Dr. Bernstein opened her own headache clinic for women, the Women’s Headache Center at Cambridge Health Alliance.
Elaine McArdle , co-author of The Migraine Brain (Copyright © 2008 by Carolyn Bernstein, M.D. and Elaine McArdle), is an award-winning journalist, lawyer with a degree from Vanderbilt Law School, and migraineur who for twenty years has been writing for newspapers and magazines, including The Boston Globe, Boston magazine, and many others.