Biology 202
1998 Third Web Reports
On Serendip

Migraine: the result of a misunderstood chemical
reaction involving neurotransmitters and vasoamines

Meredith Ralston


Approximately 16 million Americans suffer from the debilitating effects of migraine(1). This severe form of headache can range from moderate pain experienced infrequently, to an incapacitating condition which occurs regularly and impacts on work. The two main forms it occurs in are classic and common. A classic migraine is preceded by an "aura," a disturbance primarily of visual perception. People experiencing aura may have blind spots, tunnel vision, visual and auditory hallucinations, speech disturbance, ringing in the ears, numbness of parts of the body, and see flashing lights or zig-zag patterns(11). In common migraine, there is no aura. Though they are not a type of migraine, cluster headaches are commonly associated with migraine, since they are equally, if not more, severe.

The history of this condition dates back supposedly to when Neolithic "surgeons" would drill holes in the skulls of headache sufferers. Hippocrates prescribed herbs for his patients, and Galen labeled what may have been migraines or migraine-like headaches "hemicrania" because of their tendency to occur on one side of the head at a time. Willis, a British physician, used the word "migrum" instead(8). One web page described the condition succinctly as "an inherited, multi-system disturbance set off by a variety of chemical triggers."(8) Although it is now understood that migraine is a wholly biological condition, resulting from anything from hormonal changes, to bacterial infection, to fluorescent lights, originally it was thought to be a psychological disorder, and sufferers would be treated like hypochondriacs. They were thought to be neurotic, obsessive, compulsive, rigid, and suffer from repressed hostility(11). But while migraine sufferers do fit a certain physical profile-- roughly 75% are women, and it is an inherited trait(1) -- there is no mental profile associated with it. Symptoms:

Migraines vary widely from person to person. There are many common symptoms, though. The pain is moderate to severe, and can last from four to seventy-two hours. Migraines may induce nausea, and the pain will frequently be worse around one eye, or on one side of the head, with the pain sometimes switching sides or affecting both sides at once. There are also abdominal migraines, in which nausea will be experienced, but no head pain. This type is more common in children.

Migraines often affect mood as well, causing either depression or excitement prior to or during an attack. Other symptoms may include pallor, dizziness, yawning, trembling, food cravings, talkativeness or difficulty using words and numbers, abdominal distention, chilliness, dry mouth, edema, excessive sweating, tender scalp, increased urine activity, sensitivity to touch, nasal drainage and swelling, numbness, or chilliness in the extremities.(7)(6)(11)

There are also a number of types of migraine which are exceedingly rare. In hemiplegic migraine, motor and sometimes sensory deficit on one side of the body will occur beyond the end of the headache. Basilar artery migraine may result in ringing of the ears, hearing loss, vertigo, disturbance of gait, bilateral numbness/tingling of the limbs, or loss of consciousness. It occurs more frequently in women and teenagers, and pain is usually bilateral and located at the back of the head. Dysphrenic migraineurs may experience amnesia, disorientation, confusion, and agitation. They may or may not experience headache. Benign exertional headaches are usually short-lived, and brought on by physical activity including sexual intercourse, weight-lifting, or sneezing. They usually occur in people who suffer other types of migraine as well.

Causes & Physiology:

The cause of head pain in migraine is known; it is the result of a swelling of blood vessels in the head due to chemical changes in the body. But migraines may be triggered by different means in different people, and though we now know what causes the pain and what will make a certain sufferer have a migraine, exactly what causes the migraine itself is still unknown.

They may be brought on by physical movement (see benign exertional headaches above), or certain kinds of lights (esp. strobe and fluorescent), sounds, foods, or smells. Some female sufferers are subject to migraines brought on by the menstrual cycle, which means that their migraines are generally frequent and regular. Environmental factors include altitude changes, air pollution, bright sunlight, fans, computer monitors, tight headbands or ponytails, loud or repetitive noise, strong odors, and weather changes(11). A wide variety of foods may serve as triggers, as may airplane trips, allergies, birth control pills, tobacco, dehydration, hypoglycemia, physical trauma, pressure on the head, change in sleep patterns, steroids, stress, and the power of suggestion (11).

According to web site (11), most researchers agree that migraine is "definitely a disorder of cerebral blood flow, and is under the control of many (poorly understood) factors." The leading theory according to this site is that pain is indirectly caused by vasoactive amines, substances which cause inflammation of blood vessels. However, "while most agree that cerebral blood flow changes are an important feature of migraine, and the distention of the blood vessels surrounding the skull is the cause of the pain, most researchers no longer support the idea that the blood flow changes are the actual cause of migraine"(11). Other theories explore the roles of serotonin, platelets, magnesium, and reduced cerebral blood flow in migraine.

Serotonin is an amine neurotransmitter which is found in the intestinal wall, the blood vessels, platelets, and the central nervous system(11) (12) (13). It appears to control appetite, sleep, memory, learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation, depression, platelet homeostasis, motility of the GI tract, and carcinoid tumor secretion in conjunction with other neurotransmitters(12). Prior to a migraine, levels of serotonin in the blood increase, and platelets increase their adhesiveness. During migraine serotonin levels drop(11). Serotonin has also been implicated in or used to treat anxiety, depression, obsessive-compulsive disorder, schizophrenia, stroke, obesity, pain, hypertension, vascular disorders, and nausea(12).

There are a number of different types of serotonin receptors, of which eight are listed in site (12). Each is located for the most part in a different part of the body than the others, and has a slightly different function. Type one, one D, two, and three have been implicated in causing migraine, and type one receptors especially are targeted when attempting to cure migraine using serotonin agonists. This is probably because type one receptors and their subtypes are located mainly in the CNS.

Coinciding with the effect of the aura in classic migraine sufferers is spreading depression, decreased cortical activity that starts at the back of the brain and moves to the front. It is more easily induced in experiments in animals when Magnesium levels are low(11).

Change in blood flow is, of course, another cause. After experiencing spreading depression, and during the aura, classic migraineurs suffer decreased cerebral blood flow. The same has not been detected in common migraine sufferers; they experience an increase in cerebral blood flow during the headache(11). The effect of blood flow on migraines may explain why physical activity or changes in altitude could bring on or stop a migraine.

A cause which is, perhaps, slightly less typical is bacterial. A study done in Italy found that forty percent of migraine patients were infected with helicobater pylori, a bacteria which is also a factor in gastric ulcers, and possibly also in Raynaud's syndrome, coronary artery disease, and stomach cancer as well. H. Pylori induced migraines are usually common migraines. Thankfully, migraineurs suffering from this type of headache have the option of a relatively simple cure; treatment with antibiotics to cure or ameliorate the condition(4).


Now that migraine has been positively identified as a biological condition, many treatments-- which may or may not require the use of drugs-- have been found.

In the brain, when magnesium ion levels are high, very little neurotransmitter is released (13). Magnesium deficiency may result in irritability and nervousness, and has been prescribed to people suffering from depression, high blood pressure, and to women suffering hormonal migraines(14).

Other non-drug treatments include identification and avoidance of foods which trigger migraine, and biofeedback, which teaches sufferers to relax. Classic and common migraine sufferers may frequently treat migraines by sleeping in a dark quiet room, or one in which a television is turned on with the volume low. Exercise, sexual intercourse, heat packs, acupuncture, cold air, massage, vomiting, yoga, relaxation therapy, pregnancy, menopause, dust masks, and standing in hot foot baths have all been known to ameliorate migraine(11). In severe cases, none of the above might work, but if migraines can be brought on by the power of suggestion, it is conceivable that mental relaxation could get rid of them.

Currently, however, researchers are excited about the possibilities offered by using serotonin and dopamine in the forms of drugs such as Sumatriptan and D-H-E 45. Peroutka suggests using dopamine antagonists with serotonin agonists, with the end goal of decreasing inflammation, increasing dopamine, and decreasing serotonin. Sumatriptan is a serotonin agonist(10). Just using serotonin agonists is not a complete answer, though; Stimulation of [serotonin] type 1 receptors by medications hastens recovery. [serotonin] agonists seem ineffective during migraine aura and fail to correct brainstem pathology as seen in positron emission tomography (PET) scans. Headache recurrence may be as high as 50 percent using [serotonin] agonists alone.(10)

Therefore Peroutka experimented with dopamine as well, hypothesizing that an increase in dopamine could trigger migraines, since it is a factor in controlling cerebral brain flow, nausea, emesis, and gastric motility. Administering a dopamine agonist to migraineurs produced symptoms of migraine, such as yawning, mood changes, nausea, gastrokinetic changes, vomiting, and dyskinesia. This is the rationale for trying to block or lower dopamine, and increase serotonin or stimulate serotonin type one receptors as a cure for migraine. Incidentally, or perhaps not so incidentally, this is a similar strategy to that used to treat hypertension with blood pressure and cholesterol lowering agents(10). This is a method which can ameliorate even severe and menstrually induced migraines.

Associated conditions:

Given that migraines are a "multi-system disturbance," an inherited biological condition whose sufferers fit a physical profile, Migraineurs as a group tend to be subject to other physical ailments, ranging from simple annoyances like motion sickness to more serious health risks.

Among these ailments are other kinds of headaches. The garden-variety tension headache is associated with an inability to relax scalp and neck muscles, and low serotonin. In contrast, one would assume, to migraines, they become more painful with vasoconstrictive drugs and less so with vasodilators. Migraine sufferers also are more likely to suffer ice pick headaches, short but intense bursts of localized head pain<11>. This seems to imply that migraine sufferers are in general more susceptible to disruptions of pain and blood vessel controlling chemicals located cerebrally.

More threatening is the higher incidence of stroke in migraine sufferers. Results of studies done especially on women and stroke showed that of women under 35 who had no common stroke risks, such as high blood pressure, or migraine, and did not smoke or use the birth control pill,1.3 women per 100,000 suffered ischemic stroke in a year. The rate for women of the same age who experience common migraine is 4 per 100,000 per year, and common migraineurs (migraineuses?) between 35 and 45 have a risk of 11 per 100,000.

For women with classic migraine who are under 35 the risk is 8 per 100,000, and between the ages of 35 and 45 this rate increases to 22 per 100,000 per year. Though these rates are not alarmingly large, female migraine sufferers would do well to eliminate other factors which increase risk of stroke(5).


Though there are a number of common symptoms for all sufferers of migraine, there is a wide range of different kinds of migraines, all having different effects on the brain and body. It's an interesting condition, because a simple, everyday stimulus such as a fluorescent light can cause such a drastic reaction. In addition, it has the possibility to affect functions such as memory and speech.

The relation between migraine and other conditions, such as depression, high blood pressure, stroke, and motion sickness is probably the key to discovering what exactly happens during migraine, and why. Also important is the role that serotonin, dopamine, and other neurotransmitters and vasoamines play. Seemingly, through their failure to effectively maintain the normal state of the body, they are the key to this pain. Once the role that serotonin plays in depression, tension headaches, and other conditions has been further studied, it may be discovered what causes the brain to start this chemical reaction, and why such innocuous seeming triggers could set it off.














13. Foundations of Neurobiology, Fred Delcomyn; W.H. Freeman and Company, New York, 1998


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