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.
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The Electrical Aspect of Migraine
The abnormal electrical activity in your brain during a migraine may explain some symptoms such as vertigo, fatigue, and difficulty with thinking clearly. Some folk remedies treated this aspect of migraine. An Egyptian medical scroll dating back at least 1,500 years BCE recommended treating migraines by using an electric catfish. In other cultures, electric eels were wrapped around a migraineur’s head to ease the pain. These treatments may have helped by regulating electrical impulses that misfire during a migraine attack. Of course, you shouldn’t use anything electrical to treat yourself for migraine pain—other than a heating pad for your lower back, which may feel good if you’re achy during a migraine.
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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. See Ch. 9. Studies show that some people may respond to one triptan but not another, so if one doesn’t work for you, ask your doctor about trying another.
During a migraine attack, other metabolic factors also are involved. Many migraineurs have lower-than-normal levels of magnesium, a mineral that helps regulate nerve cells and affects how calcium behaves, both of which are related to the triggering of CSD. Magnesium is also involved in the regulation of serotonin, which would explain why magnesium supplements may help some migraineurs. See Ch. 11. There appear to be malfunctions in calcium channels in some migraineurs, which help regulate the flow of calcium into the brain and the release of serotonin. This may help explain why some calcium channel blockers can be an effective treatment for some migraineurs.
Migraineurs may also have abnormalities in the processing of the neurotransmitter dopamine, which can be another factor triggering CSD. Before a migraine attack, your levels of dopamine—involved in the regulation of the brain’s blood flow—may be higher than normal. Some migraine symptoms, including nausea, vomiting, mood changes, yawning, and fatigue, may be related to this increase in dopamine. And migraineurs may have differences in the way their bodies handle norepinephrine, a neurotransmitter that affects nerve cell function, contributing to CSD.
How does a migraine attack end? We’re not exactly sure. It’s possible that, with the passage of time, the brain finally is able to reset itself.
Questions for the Doctor
“Why Am I Susceptible to Cortical Spreading Depression?”
People with familial hemiplegic migraines appear to have one of several gene mutations that make them more susceptible to CSD. Other migraineurs may have a spontaneous gene mutationtion or one that was inherited. It’s also possible that environmental factors can lower the threshold for CSD. It turns out that women may be more susceptible to CSD than men. Women get migraines at a much higher rate than men, and fluctuations in estrogen during the menstrual cycle explain some but not all of these gender differences. According to a breakthrough study conducted recently at UCLA, women may have a much lower threshold for CSD. The study found that female mice were much more susceptible to CSD than male mice, and that this difference was independent of the menstrual cycle of the mice. A much higher strength of stimulus—two to three times higher—was needed to trigger CSD in male mice.
“My Scalp Is So Sensitive During a Migraine. What’s Happening?”
At the start of a migraine attack, many migraineurs experience a strange sensitivity in the scalp or face, or perhaps the legs or other parts of their bodies. This sensation may feel like heat or tingling or extreme sensitivity. Your scalp may feel sore to the touch so that brushing your hair is painful, a hat may feel uncomfortably tight on your head, and your clothes may feel tight. Your head or body may feel hot. This physical sensitivity is called allodynia, and it’s a very important marker during the progress of a migraine. We’re going to learn how to use allodynia as a cue to immediately take your migraine medication or begin another treatment such as biofeedback, to stop the chain reaction before a full-blown migraine attack is under way.
What causes allodynia? The most current research has found that repeated migraine attacks lead to allodynia, since frequent headaches cause people to process pain differently. That means that the more migraines you have in your life, the more pronounced allodynia may become over time.
The Trigeminal Nerve
Let’s take a closer look at one of the most important factors in a migraine: the trigeminal nerve.
Has the throbbing pain of your migraine ever run along a distinct path down the side of your face? Perhaps you could even draw a line along where the pain courses. You are feeling your trigeminal nerve, which plays a key role in the migraine process. Your brain itself doesn’t have any pain receptors. When you feel migraine pain in your face and head, it comes from the trigeminal nerve.
Humans have two trigeminal nerves, one on the left side and one on the right. The nerve starts behind the ear and then runs alongside the face before separating into three distinct branches: one up toward your forehead, one straight ahead to your nose, and one down into your jaw.
When a migraine attack begins, the trigeminal nerve gets angry and begins the throbbing and pounding along your face and head, causing the severe pain that migraine sufferers know too well. That’s why your eye may hurt during a migraine—it’s feeling the top branch of the trigeminal nerve as it throbs with each beat of your heart. Or you may feel the pain in your jaw or nose.
For more than half of migraineurs, only one of the two trigeminal nerves responds in the migraine chain-reaction, so they feel the pain on only one side of their face and head. In fact, the word “migraine” is from a French word that’s a derivation of the ancient Greek word “hemicrania,” meaning one side of the head. But many people get migraine pain on both sides of their head, which is one reason doctors—who may believe a migraine must be one-sided—can misdiagnose the problem. Which
side of your face will feel the pain? It may change with each new headache. For some people, the pain switches from one side to the other within a single migraine attack, as the twin trigeminal nerves take turns participating in the chain reaction.
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The Migraine Brain Even Looks Different
Until very recently, doctors believed that Migraine Brains didn’t look any different from other brains on a CT scan or a routine MRI. But researchers at Massachusetts General Hospital recently made a remarkable discovery: not only are Migraine Brains different, but you can actually see the differences on a brain scan, at least among chronic migraine sufferers. The somatosensory cortex—the part of the brain that processes pain, touch, temperature, and other sensory information—was 21 percent thicker in migraineurs than other people, they found. (The brain scans were performed on twenty-four migraineurs who’d had about four migraines a month for twenty years.)
Researchers don’t know yet whether frequent migraines cause this noticeable thickening of the somatosensory cortex or whether a thick cortex leads to migraines.
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For many migraineurs, the throbbing pain of the migraine is almost unbearable. It can feel like an ice pick is being jammed in and out of your eye or nose or jaw, the pain pulsating with each beat of your heart. When I explain to patients that the trigeminal nerve is responsible for this awful sensation, they often ask me a reasonable—if somewhat desperate—question: Why can’t they have the nerve surgically altered or removed?
People who suffer from a condition called trigeminal neuralgia, a facial nerve pain condition, sometimes choose to have the trigeminal nerve surgically altered. The treatment isn’t always successful and it carries a certain amount of risk, as does any surgical procedure. I don’t think this kind of surgery is a good option for migraineurs, and I don’t recommend it. For one thing, altering the trigeminal nerve may stop the pain but it won’t stop the other symptoms that are part of migraine. And because you have a trigeminal nerve on either side of your face, you’ll have to have surgery to alter each one. It’s also possible that you’ll continue to feel pain even after the nerve is altered, like people who lose arms or legs but continue to feel pain in the phantom limb.
There are surgeons in the United States who perform this surgery to treat migraine. In my opinion, this is a radical move with questionable results. Instead of such a dramatic and risky option, it’s better to try to prevent your migraine from arising in the first place, and to intervene early in the migraine chain reaction so the trigeminal nerve never gets involved. I believe you can feel much better without surgery.
Migraine and Seizure
Having migraines does not increase your risk of having a seizure disorder (also known as epilepsy), an illness caused by abnormal electrical activity in your brain. There is some connection between migraine and seizure but it’s not clear precisely what it is. The two conditions share some similarities: Seizures, like migraines, are episodic (meaning they come and go), with focal neurology symptoms at times (meaning they affect certain parts of your body like your vision or ability to walk), and we sometimes use seizure drugs to treat migraine. But the two conditions are very different in many ways, and there is no significant evidence that you, as a migraineur, will develop a seizure disorder.
However, anyone can develop a seizure disorder. If you are concerned that you may be having seizures, talk to your headache specialist. Make sure you tell your doctor if you have a family history of seizure. He or she can analyze your symptoms to see whether you are at any risk for seizure (which, let me emphasize, is rare). He or she will order tests—such as an EEG, a brain wave test—to determine whether you are having seizures.
The Genetic Link
If you have a Migraine Brain, you probably inherited it. And if you suffer from migraines, there’s a good chance one or more of your children will, too. Researchers are working to understand genetic transmission of migraine and have already found the inherited genetic mutation for certain rare types of migraine. There is more research under way to identify other genetic links.
You may have a family history of migraine that you don’t realize. Perhaps one of your parents suffered from migraines as a child or young adult but the illness resolved before they were aware of it. It’s also highly possible that your parent was never correctly diagnosed with migraine. If your mother or father had “sick headaches” or “sinus headaches,” they actually may have had migraines.
The Heart–Migraine Connection: “PFO”
In some people, migraines may be related to an abnormality in their hearts, and a number of studies are under way to further explore this connection and develop new treatments.
About 25 percent of Americans have an opening between the upper chambers of their heart called a patent forman ovale (PFO). This opening is supposed to close in newborns around the time of birth. When it doesn’t, blood that’s supposed to travel to the lungs may instead be directed toward the brain or elsewhere in the body; one consequence may be the transporting of blood clots to the brain.
In recent years, doctors have found that a large percentage of people with PFOs also get migraines. It may be that significant amounts of serotonin, which occurs in other parts of the body and is a very potent chemical transmitter in the brain, may be passing into the brain when they should be filtered out. Or it may be that impurities that aren’t being filtered out are making their way to the brain and setting off the biochemical reaction in a Migraine Brain.
Although controversial, some new studies have suggested that surgically closing this opening in the heart can completely eliminate or significantly reduce migraines for many people. New procedures mean surgeons no longer have to perform open-heart surgery to close the PFO, which makes it a much less risky operation. There are several clinical trials under way right now to further explore this potential treatment, especially for patients with severe migraines that aren’t responding to other treatments. Still, there is much more research to be done before this becomes be a mainstream option for migraine patients, especially as any surgery carries with it significant risks.
Remember, there is no “cure-all” for migraine that works for everyone. You can talk to your doctor about PFOs, discuss whether you want testing to determine if you have a PFO, and discuss your options from there. But there is no guarantee that closing a PFO will terminate your migraines.
Your Migraine Brain May Change Over Time
“We just got back from France, and my mother had a great time trying wines. Her whole life, she was never able to touch wine because of her migraines. But now she’s eighty-three, and something in the last couple of years has changed, and nobody seems to know what that is. Now she can drink wine without any problems. It’s nice for her, toward the end of her life, to be able to enjoy it.”
—Maggie, 45, financial consultant
One of the more challenging aspects of managing your migraine is that its characteristics may change. Over time, you may get more attacks or fewer, the symptoms may vary, the pain may get worse or better, and old triggers may stop bothering you while new ones crop up. We don’t know why migraine patterns often change. If your migraine attacks decrease after menopause, that makes sense, since your hormones stop fluctuating. But why isn’t that true for all women? And why do some women find their migraines get worse after menopause? These are among the many eccentricities of migraine that we don’t yet understand but are continuing to study.
It’s important to stay on top of changes in your migraine pattern because you may need to change your treatment plan, too. Medicines that once worked may stop helping you. Your Migraine Brain may react to triggers that never used to bother you, so you’ll have to adjust your wellness plan to try to avoid them.
I have a patient who had migraines related to her period since she was in her teens. The attacks were fairly mild and lasted one day, at the most. But a terrible incident in a hospital seems to have changed her migraine patterns. When she was in h
er early forties, she generously agreed to donate a kidney to someone in desperate need. While she was under general anesthesia, an epidural line into her spine dislodged and the chemicals soaked her bed linens. She lay in them for hours and sustained severe, first-and second-degree chemical burns down the right side of her body.
From that point on, the characteristics of her migraine changed dramatically. For the next eighteen months, she had a severe migraine every single day without a break. She’d feel like she was going to pass out and couldn’t walk straight. She ended up in the emergency room every few months and missed countless family events and work days. She was absolutely desperate. When she became my patient, we started an aggressive treatment plan. Her migraines are down to one a week, and the symptoms are much less severe.
The Migraine Brain Page 6