Studies of migraine’s many triggers offer paths to new therapies

He also tried levcromakalim, another blood vessel opener that lowers blood pressure. It’s a potassium-channel opener, and this, too, caused migraine attacks for all 16 people in the study.

To Ashina, these experiments suggest that medicines that turn off migraine-inducing pathways at or before the point of potassium release could be of benefit. There might be side effects, such as changes in blood pressure, but Ashina notes there are potassium-channel subtypes that may be limited to blood vessels in the brain. Targeting those specific channels would be safer.

“I personally really like the potassium-channel track,” says Russo. “I think if we can find drugs targeting the ion channels, the potassium channels, that will be fruitful.”

Hopeful for opioids

Russo is also upbeat about work on a new kind of opioid. Traditional opioids, whether from poppies or pharmacies, work on a receptor called mu. Along with their remarkable pain-dulling abilities, they often create side effects including constipation and itching, plus euphoria and risk for addiction.

But there’s another class of opioid receptors, called delta receptors, that don’t cause euphoria, says Pradhan, who’s investigating them. When delta-targeting opioid molecules are offered to animals, the animals won’t self-administer the drugs as they do with mu-acting opioids such as morphine, suggesting that the drugs are less pleasurable and less likely to be habit-forming.

Delta receptors appear in parts of the nervous system linked to migraine, including the trigeminal ganglia. Pradhan has found that in mice, compounds acting on the delta opioid receptor seem to relieve hypersensitivity to touch, a marker for migraine-like symptoms, as well as brain activity associated with migraine aura.

Encouraged by early evidence that these receptors can be safely targeted in people, two companies—PharmNovo in Sweden and Pennsylvania-based Trevena—are pursuing alternative opioid treatments. Migraine is one potential use for such drugs.

Thus, the evolving story of migraine is one of many types of triggers, many types of attacks, many targets, and, with time, more potential treatments.

“I don’t think there’s one molecule that fits all,” says Levy. “Hopefully, in 10, 15 years, we’ll know, for a given person, what triggers it, and what can target that.”

This story originally appeared in Knowable Magazine.