Sex on the brain. Women who have migraines have thickening in two brain regions: the insula, shown here in the back left side of an average brain, and the precuneus, shown here in the right hemisphere viewed from the middle. Areas of yellow show th

Nasim Maleki

The science of migraines

SAN JOSE, CALIFORNIAIf you've ever had a migraine, you know it's no ordinary headache: In addition to throbbing waves of excruciating pain, symptoms often include nausea, visual disturbances, and acute sensitivity to sounds, smells, and light. Although there's no cure for the debilitating headaches, which affect roughly 10% of people worldwide, researchers are starting to untangle their cause and find more effective treatments. Here today at the annual meeting of AAAS (which publishes Science), Science sat down with Teshamae Monteith, a clinical neurologist at the University of Miami Health System in Florida, today to discuss the latest advances in the field.

Q: How is our understanding of migraine evolving?

A: It's more complicated than we thought. In the past, researchers thought of migraine as a blood vessel disorder, in part because some patients can feel a temple pulsation during a migraine attack. Now, migraine is considered a sensory perceptual disorder, because so many of the sensory systems—light, sound, smell, hearingare altered. During an attack, patients have concentration impairments, appetite changes, mood changes, and sleeping is off. What fascinates me is that patients are often bothered by manifestations of migraine, such as increased sensitivity to light, in between attacks, suggesting that they may be wired differently, or their neurobiology may be altered. About two-thirds of patients with acute migraine attacks have allodynia, a condition that makes people so sensitive to certain stimuli that even steam from a shower can be incredibly painful. One way to view it is that migraineurs at baseline are at a different threshold for sensory stimuli.

Q: What is the most cutting-edge treatment today?

A: The mainstay acute treatment for migraines are a class of drugs called triptans, which act on serotonin receptors. Serotonin is thought to be the underlying neurotransmitter involved in migraine, based on a lower than normal level of serotonin (5-HT) which increases during attacks. There's also a strong relationship between depression [which is linked to abnormal serotonin levels] and migraines: People with depression are more likely to get migraines, and people with migraines are more likely to be depressed. It's not entirely clear how triptans work, but they are able to abort attacks in some patients. They are wonderful drugs, but not everyone responds. The field is now wide open for new drug targets, especially ones that do not constrict blood vessels like the triptans.

Q: What are some promising new treatments?

A: One new drug targets a substance called CGRPcalcitonin gene-related peptidethought to be one of the peptides that's released during an acute migraine attack. A multicenter, randomized, double-blind placebo-controlled preventive study [in which different doses of the CGRP-targeting drug, telcagepant, were given to people with migraine] showed some liver enzyme abnormalities in a small subset of patients so it failed to pass the safety requirements although the data suggested a potential role. But now there's an antibody version that has completed the phase II studies and is considered the hottest new thing in the field. It was too small of a trial to really determine effectiveness, but it is still really exciting because it's the first trial which suggests that a drug which targets CGRP can be safe.

Q: To what extent is migraine inherited?

A: The genetics need some work because migraine so complicated, but for most patients we're able to tie it to a family history. As a medical resident in 2008, I learned about three genes associated with hemiplegic migraine, a condition in which people go weak on one side. Now, a number of additional genes have been associated with migraine. Some are associated with glutamate, a neurotransmitter associated with excitatory functioning. A lot of brain systems utilize glutamatea major excitatory neurotransmitterso blocking it may have some challenges.

Q: What risk factors have you found for migraine?

A: Migraine usually presents itself in adolescence or preadolescence; women are more likely to have migraines around their menstrual cycles and the headaches seem to happen in response to hormonal changes in men as well. Low socioeconomic status as well as obesity, and poor sleep also increase the frequency of attacks. Lesions in brain tissue called infarctions are complications of migraine, and risk factors such as smoking and oral contraception may increase the risk. 

Q: What are some challenges to studying migraine in the brain?

A: Right now we're stuck with animal models that don't exactly mimic the complexities of the human brain or even a migraine attack. Human brain imaging has a much greater potential and has exciting applications in migraine. With brain imaging, we are able to better understand the structures, connections, and chemicals that are involved in migraine. In addition, postmortem studies of the brains of people who have suffered migraine may be helpful in better understanding the etiology of white matter lesions commonly associated with migraine, currently of unknown etiology. However, it can be difficult to interpret such studies because what caused someone to expirestroke, cancer, etc.might change the brain.

Check out our full coverage of the AAAS annual meeting.

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