Migraines could be treated by ramping up the brain’s cleaning system

One-third of people with migraines don’t respond to current treatments, but harnessing the brain’s cleaning system could open up a new treatment option. A drug that ordinarily treats high blood pressure helped this system more effectively remove a chemical substance from the brains of mice that is a potent driver of migraines. As a result, the mice showed fewer signs of facial pain, which affects about 60 per cent of people with migraines during an episode.

Around 1 in 7 people worldwide have migraines. Pain, pressure or throbbing in the cheeks, jaw, forehead or behind the eyes are common symptoms, and can be exacerbated by even light touch. “Simply brushing their hair can be painful for [people with migraines],” says Adriana Della Pietra at the University of Iowa, who presented the research at the Oxford Glymphatic and Brain Clearance Symposium in the UK on 1 April.

Standard migraine treatments include painkillers such as triptans, which are thought to reduce inflammation and lower levels of a neurotransmitter called calcitonin gene-related peptide (CGRP) – a driver of migraines and the target of our most potent therapies against the condition. “But lots of people don’t respond to the drugs they’re offered, and quite often, people are living through hell that can last for days. Quite often, they can’t do everyday tasks,” says Valentina Mosienko at the University of Bristol, UK, who wasn’t involved in the research.

In an earlier experiment, the researchers found that prazosin – a drug that is approved to treat high blood pressure – relieves facial pain caused by traumatic brain injuries in mice. Such injuries impair the brain’s waste disposal system, known as the glymphatic system, while prazosin boosts the flow of waste fluid from brain cells through this system. However, some migraine-affected mice that the researchers used as a control also seemed to benefit.

Investigating this further, the team added prazosin to the drinking water of a group of mice for six weeks, while a separate group were given regular water. The researchers then induced migraines in all of the rodents by injecting them with CGRP.

Half an hour later, the team prodded the mice’s foreheads with plastic filaments of increasing thickness. Although none of these is ordinarily painful, the filaments are increasingly noticeable as they become thicker. The researchers found that the mice in the prazosin group could be touched by substantially thicker filaments without flinching than the control mice. The former group acted similarly to mice that hadn’t been injected with CGRP, says Della Pietra.

Further analysis showed that prazosin reversed impairment of the glymphatic system caused by CGRP, which probably enhanced its clearance and that of other molecules that transmit pain signals, says Della Pietra.

The researchers hope to test whether the same effects occur in people. “If it works in humans, that would be fantastic,” says Mosienko. “The drug is already in use, so we know it’s safe for use.”