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On the pathway to preventing migraines


As migraine sufferers know all too well, a whole variety of things can set off the headaches: stress, lack of sleep, loud noises, even eating a hot dog. The long list of possible triggers has made it difficult for doctors and researchers to figure out how and why migraines occur in the brain.

Now, a systematic review of migraine research suggests that most triggers have something in common: They induce a type of damage in the brain called oxidative stress. Interrupting that pathway could help treat or prevent the debilitating headaches, according to the work published this month in the journal Headache.


“Although we know a lot about how migraine attacks occur, there is still not complete consensus about all the events involved,” says Elizabeth Loder, chief of the Division of Headache and Pain at Brigham and Women’s Hospital in Boston, who was not involved in the study. “This is a very thought-provoking and hypothesis-generating paper.”

An estimated 12 percent of adults in the United States suffer from migraine attacks. Researchers previously proposed that migraine triggers might work by activating the sympathetic nervous system, or by making the brain more excitable, or perhaps by directly irritating pain fibers in the brain. Recently, however, scientists have found that a protein in cell membranes called TRPA1 activates nerve cells, sending pain signals rocketing into the brain, in response to a build-up of damaging molecules known as “free radicals.”

A surplus of free radicals creates an imbalance in the body called “oxidative stress,” and given the new information linking this condition to pain, Jonathan Borkum, a clinical psychologist and professor at the University of Maine, wondered if it might be a common mechanism underlying migraine triggers. He scanned through more than 2,000 scientific studies about migraine triggers, then focused on a subset of about 30 key papers on how given triggers, such as dehydration or air pollution, affect the brain.


Borkum found that almost all reported migraine triggers lead to oxidative stress, suggesting that it is indeed a common pathway for migraines. Yet in some cases the reported triggers may not cause migraines themselves, says Loder: Some people may think chocolate is a migraine trigger, for example, but it may actually be the craving for chocolate that is the warning sign of a coming headache. Scientists should therefore winnow and validate the list of triggers first, says Loder; then they will be better able to detect what the triggers have in common.

If migraines are the result of oxidative stress, it might be possible to intervene to alleviate or prevent them. Antioxidants, such as beta carotene and vitamin C, are known to bind and shut down free radicals, but may have health risks. In 2013, for example, researchers in Denmark found that several antioxidant supplements, including vitamin E and vitamin A, were associated with higher rates of death for adults who took them than those who did not. “I would not rush to put people on antioxidants to treat migraine,” says Loder.

Borkum agrees that the hypothesis is simply a starting point for more work into triggers, treatments, and why the brain reacts to oxidative stress in this way. “As with all theories, it points in the direction of more research that needs to be done.”