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As far back as the 1600s, the prominent English physician Thomas Willis suggested that headaches are caused by a rapid increase in the flow of blood to the brain. He theorized that the suddenly bulging blood vessels put pressure on nearby nerves and that these in turn trigger the pain. A variation on Willis' idea became the favored explanation for the cause of migraines. (An important network of blood vessels at the base of the brain bears Willis' name.)
Two things have occurred in the past couple of decades to alter that view. First, several imaging techniques were developed that allowed doctors to study blood flow in the living brain. Second, scientists learned a great deal more about the nerve endings that are embedded in the dura mater, the fibrous outer covering of the brain. Armed with these tools and that information, researchers concluded that the order of events in a migraine is not as straightforward as they had been taught. The nerve endings in the dura mater appear to act first, releasing proteins that cause the blood vessels to open and prime the nerves to maintain a state of alert. In other words, swollen blood vessels are the result of a growing migraine, not its cause.
Tracing the pathway of the affected nerve endings deeper into the brain led researchers to the trigeminal nerve, a complex network of nerve fibers that ferries sensory signals from the face, jaws and top of the forehead to the brain. During the course of a migraine, scientists discovered, the trigeminal nerve practically floods the brain with pain signals. The more researchers learn about the trigeminal nerve, the more they believe that it is involved in all types of primary headaches, including tension and cluster headaches. The differences in the headache types seem to stem from what activates the trigeminal nerve and how it responds.
So much is happening all at once during a migraine that it has been hard to pinpoint what sets off the trigeminal nerve. Some scientists are focusing on a wave of electrical activity that spreads across the brain just before a migraine and triggers the aura--the shimmering light show experienced by 1 in 5 migraine patients. Others wonder wheth-er there is some kind of migraine generator buried deep within the brain stem. Even when researchers think they know the order in which different parts of the brain turn on during an attack, they can't always be sure if one section is initiating an action or anticipating the need to respond.
What seems clear, however, is that the brain of a migraineur (as sufferers are called) is primed to overreact to all sorts of stimuli that most people can easily tolerate. "The brain receives input from a wide variety of triggers--stress, hormones, falling barometric pressure, food, drink, sleep disturbances," says Dr.David Buchholz, a neurologist at the Johns Hopkins University School of Medicine in Baltimore, Md. "Each of us has hisown stack of triggers and his own personal threshold at which the migraine mechanism activates. The higher the trigger level climbs above the threshold, the more fully activated the migraine system--and the more pain."