Headache Treatment


Sunday, May 16, 2010

Migraine cure? Theory, Hype, and Hope

Interview with Dr. Charles Matthews
Director, the North Carolina Comprehensive Headache Clinic
Raleigh, N.C.

Q- Dr Matthews, can migraine headaches be cured?

A- For some people, headaches are relatively mild. That is, for some it's only a little agony; for other it's a lot of agony.

Let's talk about the severely affected for a moment. For the severely affected, headache occurs daily or very close to daily, and follows a progressive course. Chronic daily headache occasionally progresses to severe impairment of daily activities- sleep disturbance, depression, generalized body pain with similarities to fibromyalgia, digestive disturbances; as I've discussed with you before, migraine headache is a a disorder involving all body systems.

Chronic daily headache progression affects your employment and your family and loved ones. Unemployment and divorce are at the end of the headache clinical spectrum. In addition to all this misery, there is an increased risk of stroke with migraine, much worse if you have a clotting disorder, if you smoke, take birth control pills or hormone replacement, or a heart structural disorder such as patent foramen ovale.

I've had many patients feel disappionted when they have an MRI and nothing shows up. "With a disease like this, why would I worry about a little cancer?". For those severely affected with chronic daily headache, it would be nice to have this problem that affects your whole body localized to one spot in your brain; even if it was cancerous, they are thinking perhaps it could be taken out. So migraine can be a terrible condition, and headache sufferers are often misunderstood

We have all heard about various potions, vitamin therapy such as vitamin B2, minerals such as magnesium and various substances and treatment modalities that claim effectiveness for migraine, some to relieve symptoms of pain and other symptoms of the migraine attack. I will also include FDA approved pharmaceuticals in this category, such as Topamax (topirimate, an anticonvulsant), Depakote (sodium valproate, another anticonvulsant), Inderal (propranolol, a blood pressure medication), Elavil (amitriptyline, an antidepressant), and Imitrex and other triptans (which are taken only to interrupt a migraine headache attack). Migraine products are a big market, and all products are inevitably associated with advertising hype.

There are new devices coming to market. One of these is a "gun" that discharges a capacitor, induces a rapid fluctuation in the magnetic field in the brain, discharges neurons, and interrupts the headache. In one clinical trial, it worked a little bit, and perhaps the technique will be optimized to be more useful. There is another device, the Argus Neurostimulator, that uses a cold laser that calms the nerves at the back of the nose, with early results showing competitive effectiveness with triptans. I am one of the scientific advisors to Argus. The Argus neurostimulator produces a nerve block, and we know though many publications in peer-reviewed literature that nerve blocks in the nose (sphenopalatine ganglion and Gassarian ganglions) work well, but the injections are uncomfortable and have side effects. Double-blind studies have been performed on both techniques, but multicenter studies have not yet been done on these devices.

I classify migraine headache therapies into two types. The first type works primarily on the periphery- that is, the nerve cells in the spinal cord, the motor nerves out to the muscles, the sensory nerves back to the nerves in the spinal cord. These are the "first order reflexes", named this way because they are the closest reflexes to the outside world. In the face, the peripheral reflex involves the trigeminal and facial nerves. In the neck, shoulders, and rest of the body, there is a motor nerve at each segment going out, and a sensory nerve coming back in, that meet in the spinal cord at that level.

The second type works in the brain, on secondary reflexes. That is, there is a first order reflex, which operates in segments up and down the body. Then, there are second order reflexes that come from the brain down to the spinal cord and back up again.

Migraine headaches can start with involvement of either peripheral or central reflexes, and spread. For example, migraine headaches involving the brain, if they occur frequently enough, can cause chronic neck pain. On the other hand, a minor neck pain, if it persists long enough, can provoke migraine headaches. For example, if you put your hand on a hot stove, it will jerk away before your brain gets a chance to realize it; so the pain produces a motor response automatically, acting through the spinal reflex. But the motor response itself can cause pain, if it persists long enough. Many people with minor headaches will strain their neck (at the gym, working too long in one posture, doing overhead lifting, or a deceleration injury such as a rear-end collision) and then their migraine headaches will get much worse. I call this a "wind-up" headache; neck pain leads to spasm, spasm leads to more pain, more pain leads to more muscle spasm...

Q- So, how do the primary and secondary levels interact?

A- Here's a pretty good analogy. Think of someone with a hearing aid at a party who can't quite pick up what people are saying. (The person with the hearing aid is the peripheral reflex in our example, because hearing is a primary reflex, closest to the outside). This unfortunate person keeps turning up their hearing aid, trying to hear the conversation. At the same time, their brain is also turning up the sensitivity, trying to hear. This occurs because no information is getting in, so the brain (the second order reflex) is turning up its own listening abilities.

Suddenly, the hearing aid squeaks, and pain occurs. Not only is the brain exposed to pain, but the brain is in a sensitive state, listening very hard for the sound. If this situation occurs a lot, the brain gets depressed and gives up listening for the sound. The same thing happens in migraine headache; there is peripheral sensitization of the trigeminal nerve, and central sensitization in the brain, and a lot of squeeking going on, including head as well as body pain. Over time, the brain gets depressed, other areas become involved, and the depression spreads. This can mean that you personally get depressed- lack of energy, loss of ability to regulate sleep. However, I think in most cases the problem starts with a brain metabolic depression and spreads to the neck, rather than the other way around.

Q- Go back to your classification of migraine therapies. You think of some migraine headache treatment as directed to the peripheral nerves?

A- That's exactly right. Triptans, pain medications, muscle relaxers, trigger point injections, massage, and the Argus neurostimulator device have been shown to work on peripheral nerves. When they work, they work temporarily, when they are applied at the time of the migraine headache attack. That is because they interrupt the transmission in the peripheral nerve.

Q- What treatments work on the secondary reflex to the brain?

A- When headaches become chronic, the brain adapts and learns. So we take a triptan, get a massage, have trigger point injections, take muscle relaxers, and feel better for hours or a few days. But we're only feeling better on the outside; the brain is listening for the pain signal from the peripheral reflex, turning up the sensitivity. The brain says "I don't hear the pain I'm used to!" and cranks up the sensitivity. Then, you're back to getting ready for the next attack. (If you want to read about interactions of reflexes, adaptation, and sensitization in more depth, the classical work was done by Ivan Pavlov in what was then Russia many years ago).

In my view, the basic problem in chronic migraine headache is a metabolic depression in the brain, and the attacks are associated with spreading of that depression, which precipitates sensitivity of the peripheral reflexes. That's why facial sensation, as well as pathways for sensing light, sound, odors, body pain sense, become sensitive. One can even think of nausea as associated with hypersensitivity of taste. There is much more to say about this but we are limited by time today.

Treatments that work on the secondary reflex on the brain include antidepressants (which increase brain neurotransmitters) that boost brain metabolism. You can see the brain depression of migraine, as well as the boosting effect of antidepressants, on certain types of images such as PET scans.

Q- Don't painkillers and muscle relaxants also work on the brain?

A- Sure, they make you sleepy temporarily. In fact, anything that works on the primary reflexes make you sleepy, and that's clearly a central effect. Massage, for example, can put you to sleep, but it's temporary. Stimulants such as caffeine also work to stop migraine headaches. The real distinction between types of treatments is in the duration of time they are applied. Relaxants like muscle relaxers, and stimulants such as caffeine, don't effect the brain long term because the brain adapts when they are used chronically. Muscle relaxers don't work for more than a few weeks, and a caffeine habit will develop in about the same length of time.

Q-So, what matters is how long the effect is maintained?

A- Exactly right. If you have a brain metabolic depression, and you take caffeine, it will increase the brain metabolism and your headache gets better, but if you take caffeine daily, you adapt to it and then you may have headaches when you stop the caffeine. We call these "rebound headaches". But with antidepressants, the effect is continuous, and you don't adapt to them. For many people, antidepressants aren't tolerated or just don't work for headache, but they don't typically wear out in their effect.

Q- So, can antidepressants cure migraine headaches?

A- I don't think so. What happens is that you need to take the antidepressant, and that's not a cure. Often, we can get a remission of chronic daily headache, but the problem is still "lurking". And, for example, many with migraine headaches have weight gain and constipation, two problems that antidepressants tend to make worse (the antidepressants that don't cause weight gain, such as Wellbutrin, tend not to work for migraine headache or may make the condition worse). I think this comes from a simple observation- something is lacking in migraine headache, and I don't think the problem is a deficiency of Elavil.

Q- So, what do you think is lacking in migraine headaches?

A- There is a theoretical debate going on between those who feel we lack something in the environment, and those who feel we lack something in the genes. Although there is clearly an inherited tendency, the more important problem, I'm pretty sure, is a metabolic disruption. If you include hormones, I think the environment is almost always more important than genes- and you can do something about the environment.

Most of the chronic diseases of our culture are increasingly considered to be disorders of the environment affecting intermediary metabolism- heart disease, cancer, and Alzheimer's disease. The metabolic disruption occurs in the energy production areas of the cells called mitochondria. Interestingly, in research done at the Headache Clinic and with other investigators, almost all people with migraine have a high lactic acid, which is leaked by the mitochondria when you run out of oxygen and use anaerobic glycolysis. When you run up a hill, you go anaerobic, you spill lactate into the blood from the mitochondria, and then you breath hard to blow off CO2 which counteracts the lactic acid. That's why people with migraine headaches feel tired; they are physiologically running up a hill all the time, even when they don't have migraine. When we measure lactic acid it's high, and when we measure CO2 it's low. This is so common as to practically be an effective blood test for migraine headache; over 90% of patients with migraine headache in our clinic are below the 10th percentile for CO2. Migraine headache sufferers are physiologically running up a hill all the time.

Q- So, is there any hope for a permanent cure?

A- I think so. First, there are things you can do yourself. Behavioral "synchronizing pulses" are important- you must get great sleep. That's when everything is synchronously turned off, stops the spreading of the cortical metabolic defect, and allows restoration of function.

Brief high intensity exercise to tolerance helps- just two minutes, not long enough to stress you, twice daily, can help adapt your brain to higher metabolism. Walking outside is helpful (there's lots on research on the effect of light on mitochondrial production).

A whole foods diet, free of pesticides and hormones, and free of addictive substances like caffeine and sugar and flavor enhancers, is recommended (occasional caffeine, even in large amounts, is fine and can even be used to treat occasional headaches, but even a small daily habit will lead to long term increase in migraine headaches).

Controversial areas include supplementation of fat soluble vitamins, avoidance of wheat products and other dietary adjustments, and avoidance of polyunsaturated fats which have been implicated in mitochondrial disruption. You can't "sell" an optimum environment, though, so you won't hear any hype about it.

Optimizing these environmental factors is ultimately what's necessary for a cure. These things are not easy, though; if they were, we would probably have no heart disease, and possibly very little cancer or Alzheimer's disease. In the end, diet, exercise, adequate rest, and being outside in natural light are likely to be things you can do that may fundamentally change the basis for the production of headache- a cure.

Finally, while you are trying to improve your health, you can do things that assist cortical metabolism directly.

We have used thyroid augmentation for some time at the Headache Clinic, sometimes short term and sometimes longer term. There is a very large range of normal for thyroid tests, with the top normal being about 10 times greater than the bottom normal. Some people with normal thyroid function tests benefit from thyroid augmentation, and that can also relieve the fatigue, and digestive disturbance (IBS and constipation) that occur with chronic headache. Often when everything else has been tried, medications are producing side effects, and especially when every other system in the body is going wrong, thyroid augmentation for headache can be remarkably effective. At the Headache Clinic, we use the same protocol developed by Dr. Arthur Prange, a professor emeritus at UNC. Dr. Prange started the field of neuroendocrinology with his treatment of atypical depression with thyroid hormone.

Supplementing the respiratory cofactors in the mitochondria, such as with the use of the vitamin niacin (vitamin B3, also used to treat elevated cholesterol, and a respiratory enzyme co-factor), is a promising area of long-term treatment for migraine headache.

For more information, go to our website at http://ncheadaches.com.

You may also call 919-781-7423 to make an appointment at the Headache Clinic for neurological evaluation.

We are located in Raleigh N.C. close to Rex Hospital.