One in ten people worldwide experience migraine and thus occasional debilitating headaches. Despite the prevalence of the disease, little is known about the cause and triggers. Danish researchers have now shown for the first time that reduced oxygen can cause migraine. This may help to reveal the mechanism behind the recurring headaches.
Isn’t it just a headache? And can’t you just take a few aspirin and make things better? For those who have not experienced it, migraine can be an incomprehensible condition. Apparently healthy people can be incapacitated from one day to the next by multiple symptoms such as headache, nausea, blurred vision and aversion to noise, bright light or touch. For researchers, the disease’s causes are still a mystery, but now Danish researchers are getting a little closer to understanding it by inducing it experimentally.
“Previous studies have shown that people living at high altitudes more frequently experience a special type of migraine. We therefore attempted to re-create this situation experimentally by exposing people with migraine to oxygen concentrations equivalent to those at 4700 metres above sea level. The results showed that 8 of the 15 participants developed migraine symptoms after just 3 hours in the oxygen-deprived air,” explains Nanna Arngrim, a doctor and PhD student at the Danish Headache Center at Rigshospitalet.
Fourteen healthy migraine-free individuals also participated in the trial to ensure that the migraine only affected the participants who had previously had migraine. All participants were asked to breathe air with an oxygen concentration so that their blood had 25–30% less oxygen than usual. The researchers also scanned the blood vessels in their brains and measured various markers in their blood and brains.
The only physiological difference we saw was slightly enlarged blood vessels in the brain and increased concentrations of lactic acid in the brain and blood. Both effects were expected and both occurred in both the people with migraine and the controls. The major difference was that eight of the people with migraine had an attack, with three of them having a special type of migraine with aura in which people have unpleasant visual disturbances.
A wave of activity
About 30% of migraine patients have this aura phase, with severe visual disturbances in the form of colours, patterns or blind spots before the migraines. For many, this is initially a frightening experience, but fortunately it typically disappears in 30–60 minutes.
The aura condition is very interesting because it is one of the known physical manifestations of cortical spreading depression, a nervous system effect that is thought to be the mechanism behind a migraine aura. If we can induce this condition experimentally, we will probably learn about the mechanism behind migraine and thus become better at treating and preventing attacks.
Cortical spreading depression can best be described as a wave of powerful electrophysiological activity that spreads from neuron to neuron in the brain. Once the wave has passed, the neurons are virtually paralysed for a considerable time. The wave of activity requires both extra blood and energy, but the period of inactivity following the wave reduces the blood supply.
“In addition to our results showing how a lower oxygen concentration can induce migraine, they are also mainly important because, for the first time, we have tools for studying migraine with aura under controlled conditions. This is therefore an important step in understanding the condition – and a very necessary step on the way to curing migraines in the long term.”
“Migraine induced by hypoxia: an MRI spectroscopy and angiography study” has been published in Brain. In 2015, the Novo Nordisk Foundation awarded a grant to a main author, Messoud Ashina, Rigshospitalet, Glostrup, for the project Investigation of Vascular Inflammation in Migraine without Aura using Molecular Nanoimaging and Black Blood Imaging MRI.