Migraines and salt: USC neurologist connects the dots

Too many people are familiar with the throbbing pain of migraine headaches. About one in seven people have had migraines. The World Health Organization places migraine as one of the 10 most disabling medical illnesses on Earth. Unfortunately, the cause of migraines is not yet understood. As a result, lasting, dependable solutions for the condition remain elusive.

USC neurologist Michael Harrington, MB, ChB, has devoted much of his career to increasing knowledge about migraine. Along with his scientific curiosity, the needs of patients are at the top of his mind.

“I want to know what’s going on in peoples’ brains when they have migraine,” said Harrington, a research professor of neurology at the Keck School of Medicine of USC. “For a long time, I measured everything I could. Tens of millions of Americans need help, and we definitely want to help them.”

Harrington thinks that salt intake may hold a key. And he backed that idea with evidence in a recently published research letter in Headache: The Journal of Head and Face Pain. 

He highlighted findings from large studies that followed people’s diet and health for years, basic research, and studies scanning the brains of human volunteers. The letter brought to light links that tie migraine to the science of how the brain regulates sodium intake.

“It’s clear that higher levels of sodium in the brain play a major role in migraine,” said Harrington, who is a fellow of the UK’s Royal College of Physicians. “But how it plays that role is far from worked out as of yet.”

Lower-salt diet, but more sodium in the brain

The letter was spurred in part by recent research from Denmark. Using questionnaires from thousands of young adults, the study showed in part that headaches are associated with less salt in the diet. 

The findings echoed results from 2016 research led by Harrington. That study, the first to examine sodium intake and migraines, dug into data from about nearly 9,000 adult participants from the long-running National Health and Nutrition Examination Survey. It showed that a history of severe headache or migraines correlated with lower dietary sodium.

“This Danish group — a long way away, studying a different population — found the same thing,” Harrington said. “That replication is rather useful.”

In earlier research, Harrington used sodium brain imaging to monitor the brain. He found that during migraine, sufferers have elevated sodium in their cerebrospinal fluid, which circulates through the spine and brain — but not in their bloodstream. When the same participants had no headache, sodium levels in the fluid were normal.

The presence of sodium in cerebrospinal fluid is vital for brain functions, because sodium drives nerve impulses on the molecular level. Insight into how the brain keeps a steady level of sodium in the fluid within it provided another clue.

The role of salt appetite and sodium balance

Harrington’s research letter summarized neuroscience discoveries from the past few years by colleagues such as Caltech’s Yuki Oka. These lab studies uncovered circuits in the brain where specialized neurons sense sodium in pockets of cerebrospinal fluid. With too little, these cells signal other neurons that spur appetite for salt and reduce aversion to it. With too much sodium, the sensors put out signals that make low-salt foods attractive and salty foods distasteful.

All this happens through the brain’s system for rewards and the autonomic nervous system, which controls all the things the body does without conscious thought. The salt-sensing and appetite-regulating neurons sit in parts of the brain that neighbor areas involved with migraine.

Previous studies co-led by Harrington reinforce the salt-migraine connection. In lab models, adding sodium to pockets of cerebrospinal fluid triggered severe headache. Conversely, when the researchers blocked a mechanism that pumps sodium into the fluid, it protected against migraine.

“Everyone has some fluctuations of the sodium in their brains,” Harrington said. “However, not everyone gets migraine. In people who become sick with migraine, the ability to balance sodium is disrupted.”

Clues for further migraine investigations

The research letter concludes that the discoveries that more sodium in the brain reduces appetite for salt help to explain why migraine sufferers take in less salt — and they do so subconsciously.

Harrington intends to follow up on the leads covered in his letter.

One avenue for study would assess whether consciously lowering dietary sodium reduces large swings of intake that trigger subconscious responses in migraine sufferers. Harrington’s investigations into how sodium increases in the brain could improve fundamental understanding of migraine and many other fluctuating conditions that involve brain sodium, such as hypertension and mood disorders. Ongoing experiments by his team are evaluating how the sodium is controlled at its main site of production in the brain.

With many mysteries to solve, Harrington approaches his mission with determination and optimism. 

“I’m a great believer that there are explanations for every brain disorder,” he said. “We just have to find them.”

Learn more about Michael Harrington’s research.