More than 36 million Americans suffer from migraines, those debilitating headaches characterized by severe, throbbing, unilateral pain, often exacerbated by light, sound, and physical activity. Studies have shown a link between migraines and obesity. In fact, obese individuals with episodic headaches are 5 times more likely to develop chronic headaches than normal- weight patients. While inflammation is thought to play a role, the precise nature of the connection is not clear.

“All we know for sure is that obesity and migraine are associated,” says neurologist and headache specialist Ana Recober, MD. “We don’t know if it’s cause and effect, and if so, does obesity cause migraines or vice versa?” Aiming to find out, Recober has developed and conducted mouse studies to better understand the molecular ties between obesity and migraine. Her goal? To help identify novel therapeutic targets for chronic migraine.

Because obesity is known to cause inflammation, and the trigeminal system is central to mediating migraine headaches, Recober and her team designed the experiments to test the effect of obesity on the trigeminal system. Using obese mice (both diet-induced and genetically determined) and regular-weight mice, researchers stimulated the trigeminal nerves in the mice's heads and then examined their brains.

“We found increased neuronal activation in the brainstem of obese mice in response to a mild, painful stimulus that did not affect our control mice,” says Recober. In fact, the number of neurons in the trigeminal nucleus caudalis that were activated by a mild stimulus (low-dose capsaicin) was double in obese mice compared with regular-weight mice. The research also indicated signs of inflammation in the trigeminal system of obese mice. In her continuing research, Recober will investigate whether inflammation is one of the underlying mechanisms of chronic migraine. Her hope is that by identifying specific inflammatory molecules that may play a role in migraines, better treatments will be found.

Recober’s work with humans has additional important implications. As part of her research, she and her collaborators surveyed participants in the ongoing Muscatine Heart Study, which has tracked the health of some 700 patients since the 1970s. How many people who were obese as children, they asked, experience migraines as adults? The findings were significant: Children in the top 25 BMI percentile group (>75th percentile) have a 5 times higher risk of developing migraine than those in the lowest 25 percentile group. “Knowing that obesity in childhood is predictive of migraine in adulthood is important and warrants further research,” says Recober.