The Chemistry of the Brain
The precise cause of migraine headaches is not fully understood, but it is generally believed that the key element in understanding them has to do with the blood flow changes in the brain. The theory favored by many researchers reveals that a certain vulnerability in the nervous system is present in migraine sufferers that is not present in non-migraine sufferers. A brief study in neurotransmitters is required to understand how a migraine actually occurs.
Many researchers believe that the nervous system responds to a trigger from an outside source (food, activity, etc.) that creates a spasm in the nerve-rich arteries at the base of the brain. This spasm closes down or constricts several arteries supplying blood to the brain, thus reducing blood flow to the brain. Simultaneously, platelets clump together and are believed to release a chemical called serotonin. (The trigeminal [5th cranial] nerve has been implicated.)
The Molecular Structure of Serotonin
The serotonin causes the blood vessels in the head to contract and lowers the pain threshold. Before a migraine episode, serotonin levels have been detected to be unusually high in the brain, lending weight to the previous explanation. During a migraine attack, serotonin levels become very low. The low amounts cause the blood vessels to be unusually large. These expansions are thought to cause the throbbing pain in the temple or behind the eye. The area around the expanded blood vessels becomes inflamed and irritates the nerve endings. These dramatic changes in serotonin level and reduced blood flow may be the cause of not only the head pain, but also the nausea and distorted vision or speech that often accompanies a migraine.
The head at the top shows the brain before a migraine. The one at the bottom shows how the blood vessels become inflamed, irritating the nerve endings around them and causing pain.
According to this description, the chemical serotonin seems to be key in fully understanding migraines. Serotonin is a biogenic amine that can cause either vasodilation or vasoconstriction in central and peripheral vessels. Like all amines, serotonin is basic because of the lone elctron pair on the nitrogen that can accept a hydrogen ion in the same way that the one pair on the nitrogen in ammonia does. This may be key in understanding why such dramatic changes can occur when the levels of serotonin fluctuate in the brain. If the pH in the brain is slightly changed because of the addition or subtraction of the basic substance serotonin, the effects can be serious. Any change in pH in the body can have serious effects, and the answer to this problem may be in the creation of a drug that would be a strict buffer in the brain which would not allow any change in pH, even if the serotonin levels change. This will be discusses more extensively in "Suggestions for Research".
Serotonin, 5-HT or 5-hydroxytryptamine, and its receptors are the focus of most migraine research and drug development. As is the case for most neurotransmitters, serotonin has a relatively simple chemical structure and is found in three main areas of the body: the intestinal wall, blood vessels and the central nervous system. It seems to have a number of effects in the body, even though an average adult human only possesses about 10 mg of 5-HT.
How does 5-HT behave?
All chemical neurotransmitters (CNTs) produce their effects as a consequence of interactions with approprioate receptors. Like all others, serotonin is synthesized in brain neurons and stored in vesicles. When it receives an appropriate nerve impuse, it is released into the synaptic cleft, where it interacts with various postsynaptic receptors. Serotonin is thought to have 15 receptors and receptor sub-types: 5-HT1 through 5-HT7 as well as 8 other subtypes which are all located in the cerebral cortex, posterior hypothalamus and central grey metter. The 5-HT1, 5-HT2, and 5-HT3 receptors (especially 5-HT1) have been identified as being responsible for most of the migraine activity.
Succinctly, here is how all of these pieces fit together to cause a migraine: A nerve impulse from an outside source (a trigger) causes the release of serotonin. Then, this neurotransmitter comes into contact with the 5-HT1, 5-HT2, or 5-HT3 receptor, a person who has an abnormality or extreme sensitivity will develop vasodilation of the blood vessles in the head, resulting in a migraine headache.