The Biochemistry of Migraine Headaches



In recent years, there has been a dramatic shift in thinking among researchers about the pathogenesis of migraine headaches. Historically, physicians have assumed the throbbing, one-sided depression characteristic of migraine was caused by changes in the size of blood vessels in the brain. When these blood vessels constricted, neurological symptoms -- mood changes, visual and gastrointestinal changes -- resulted. When the vessels dilated, a throbbing headache occurred.

New research views these blood vessel abnormalities and other characteristics of migraine as symptoms of an underlying brain chemistry disorder, rather than the cause of migraine. "Now that we're using applied science in the field of headache, we're finding that, in large measure, we've had it all wrong," says Joel R. Saper, M.D., president of the American Association for the Study of Headache and founder/director of the Michigan Head Pain and Neurological Institute. "Clinical studies have now identified migraine -- and all other headache disorders -- as an illness of altered chemistry that causes both mental and physical symptoms."

Details of this altered brain chemistry are still being explored. Although several key players have been identified -- heredity, neurotransmitters, brain stem and hypothalamus -- exactly how they interact, to cause migraine is still under investigation. Here's a look at the latest thinking.


Close to 90 percent of migraine sufferers have at least one family member -- parent, aunt, uncle or grandparent -- with migraine. This points to a strong hereditary component in the disorder. According to Ninan T. Matthew, M.D., director of the Houston Headache Clinic and chairman of the 1991 International Headache Congress, as many as 50 million Americans may be "genetically prone" to headache.


At this point, scientists are making advances that will improve our understanding of migraine causation in a susceptible individual. Several factors appear to be involved:

Neurotransmitters: Disturbances in circulating serotonin or in the function of its receptors may be at least partially responsible for the vasoconstriction that leads to the aura experienced in classic migraine. During the aura stage, the sensory portion of the brain is starved for blood because the vessels are constricted; this constriction probably underlies the visual anti auditory disturbances associated with the aura (which occurs in 10 to 15 percent of migraine attacks).

In addition to causing vasoconstriction, serotonin also affects mood. In migraine, levels of circulating serotonin are usually high prior to an attack (which may correspond to vasoconstriction) and fall dramatically during an attack (which may account for the depression that occurs during anti after a migraine headache).

Pain perception is influenced by serotonin and other neurotransmitters, including endorphine and noradrenaline. Problems in the production anti function of these neurotransmitters may in some way account for the headache pain.

Hypothalamus: This part of the brain -- located behind the eyes anti above the pituitary gland -- controls body cycles, appetite, sleep, hormonal secretion anti periodic events such as menstruation. Some researchers believe that intermittent disturbances of the hypothalamus may account for some migraine symptoms, as well as the cyclical aspect of the attacks.

Brain Stem: The hypothalamus also communicates with the brain stem, the stalk that connects the cerebral hemispheres to the spinal column. The brain stem contains an anti-pain system that prevents the body from perceiving incoming stimuli as painful. Normal pain modulation occurs as a result of an interplay between our pain sensors anti the anti-pain system -- and this interplay is in some way dependent upon the proper production anti functioning of the neurotransmitters, serotonin, endorphin anti noradrenaline. According to one theory, a breakdown in the interaction between pain sensors anti the anti-pain system may account for the pain experienced during a migraine attack.


In childhood, the incidence of migraine is equally divided between boys and girls. After puberty, however, women are three times more likely to suffer from migraine headaches than men. This fact, coupled with several studies, implicate changing levels of hormones -- particularly estrogen -- as a key factor in precipitating migraine attacks. The following hormonal milestones influence migraine headache:

Menarche: Women whose migraine onset occurs at the time of menarche (approximately 20 percent) appear to have a greater likelihood of experiencing menstrual-related migraine. They also experience relief from migraine during pregnancy.

Menstrual Migraine: Women who suffer from premenstrual syndrome and whose periodic menstrual complaints include fluid retention and breast discomfort are more likely to have a menstrual-related migraine attack.

Pregnancy: Approximately 75 percent of patients with migraine improve by the second or third trimester of pregnancy; improvement may be more pronounced during a first pregnancy.

Menopause: Although migraine attacks have long been assumed to diminish during menopause, several studies suggest otherwise. Estrogen replacement therapy, often recommended as a hedge against osteoporosis in post-menopausal women, may hinder migraine improvement.

Hysterectomy: Some migraine sufferers have been advised to undergo hysterectomy to reduce the frequency and/or severity of attacks, but there is no scientific justification for this recommendation. This is especially true when estrogen replacement -- which can act to perpetuate the migraine process -- is prescribed.

Birth Control Pills: Many women experience their first migraine attack after they begin taking birth control pills. Women who have had attacks prior to taking oral contraceptives often find that attacks increase in frequency and/or severity when they use these pills. The ratio of estrogen to progesterone in birth control pills may affect their influence on migraine.


Various other migraine triggers have been identified. These triggers don't necessarily precipitate a migraine attack in all sufferers; nor does their elimination necessarily lead to a reduction in attacks in all cases. Also, the degree of a migraine sufferer's susceptibility to these triggers may vary at different times of the day or month. However, since many people with a biological propensity to migraine are helped when they limit these influences, avoidance of triggers is usually included as part of a treatment plan.

Emotional stress: Prolonged stress, anxiety, depression and suppressed hostility are powerful feelings that can induce a migraine attack. While some people experience an attack during the height of emotional stress, many also succumb to migraine headache during the letdown period -- after the stress has passed.

Diet: More than 20 percent of migraine headaches can be traced to dietary triggers in sensitive individuals. Culprit foods include those that contain tyramine (chocolate, aged cheese, chicken liver), nitrites (in smoked and cured meats), monosodium glutamate (in prepared or Prepackaged foods); phenylalanine (in artificial sweeteners), alcohol (contains tyramine and also dilates blood vessels) and caffeine (in excess for the individual).

Although these foods are believed by some sufferers to influence migraine, they may have no effect on a particular person with migraine. Nor is the mechanism by which they precipitate an attack understood as yet. Monitoring the diet and staying alert to a possible trigger (i.e., every time a particular food is consumed, a headache follows) is the best way for individuals to gauge dietary influences on the occurrence of migraine headache.

Sleep: Irregular sleep patterns, too little or too much sleep, and daytime napping have all been implicated in provoking migraine. The mechanism by which sleep influences migraine is still being explored. Such factors as the metabolic changes that occur during sleep, alternations in respiration, oxygenation and glucose levels and intense emotional experiences during dream states should be considered as possible precipitants.

Environmental factors: Changes in weather, dazzling sunlight, powerful odors, high altitudes and motion (traveling in a plane, bus, car, train or boat) may also trigger migraine.


Migraine treatment plans vary depending upon the frequency and severity of attacks. Generally, they encompass both medical and non-medical interventions.

Many attacks can be prevented by lifestyle modification. The first step is to identify and avoid triggers. This can be accomplished by keeping a diary and noting when attacks occur, how severe they are, how long they last and what happens prior to an attack (e.g., eating a specific food, experiencing emotional stress, lack of sleep).

Other preventive strategies include maintaining a regular sleep/wake schedule, eating a well-balanced diet, reducing stress through regular aerobic exercise, doing relaxation exercises and/or participating in biofeedback exercises.

Preventive medication may be prescribed when attacks are frequent (more than twice a week) and severe enough to interfere with daily functioning. These medications include beta blockers, which prevent vasodilation; calcium channel blockers, which prevent vasoconstriction and blood vessel spasms; and tricyclic antidepressants, which inhibit pain perception.

Medications that treat migraine symptoms and/or help abort an attack may also be prescribed. The major drugs used in acute attacks are the vasoconstrictors, which constrict the blood vessels and thus reduce migraine pain.

Two such drugs are currently under investigation, DHE-45 (a form of dihydroergotamine) and sumatriptan. In addition to stimulating vasoconstriction, both DHE-45 and sumatriptan appear to bind with specific serotonin receptors and thereby inhibit migraine pain. Sumatriptan appears to be a more selective agonist than DHE-45, and may produce fewer side effects. However, a nasal form of DHE-45 may be available in the near future. This type of formulation would bypass the stomach, and subsequently, would be well tolerated by migraine sufferers who tend to experience gastrointestinal disturbances.

Other medications used to reduce migraine symptoms include analgesics (over-the-counter and prescription), narcotics and non-steroidal anti-inflammatory drugs.

American Council on Science and Health, Inc.


By Marilynn Larkin

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