What happens in your brain during a migraine attack?

Migraine is a neurological disorder that affects millions of people worldwide. Centuries-worth of research into this complex clinical entity is continuing to give birth to new hypotheses. The last few decades in particular have unearthed a number of crucial insights. We now know that migraine has a genetic basis and that a host of hereditary factors are involved in causing it. But despite intensive research efforts, we still don’t understand all the ins and outs of migraine, how it develops, and the underlying mechanisms involved. This article shows where the research is at on what happens in your brain during a migraine attack.

Making waves in the brain

Recent publications have been taking a closer look at the sequence of events in migraine with aura. Sensory innervation of the meninges (layers of membranes protecting the brain) is now considered a key player in the pain process. Previous research identified a spreading wave of nervous excitation in the cerebral cortex in the run-up to a migraine attack. “Cortical spreading depression” (CSD) is the term neurologists use to describe the phenomenon. Although first described back in 1944 by a Brazilian scientist, Aristides P. Leão, it took decades of research – and the availability of powerful measurement tools – to confirm that CSD really happens.

Direct link with a migraine attack

In CSD; excited nerve cells all start (mis)firing at once, wasting huge amounts of energy. This may be why there is a lull in synapse activity (signal transmission) after such an event. The brain is in a temporary state of exhaustion. Blood flow to the brain is reduced too, a phenomenon that has long been known to trigger migraine attacks. Researchers now believe there is a direct link between the CSD event and a migraine attack. The meningeal nerves are closely connected to the areas where CSD happens, and this connection is believed to drive the process.

Overactive nerve cells

These meningeal nerves are thought to be extra active in migraineurs. Moreover, the science is clear that the neurons in the cortex of migraineurs are exceptionally excitable and super-responsive to incoming sensory information. This hyperexcitability has been reported in numerous studies. In a subset of patients – the theory goes – this state of affairs drives CSD (see above) and sets the scene for a migraine attack.

Aura and attack

The temporal proximity between aura and migraine attack led scientists, almost 40 years ago, to propose a link between the aura and pain phases in migraine with aura. Extensive research since then has gone into examining the connection between CSD, aura, and onset of pain. Today, aura is thought to be part of the CSD phase preceding the migraine attack. Because when the CSD crosses the visual center, that’s when the optical illusions and distortions (scintillating scotoma) typical of migraine with aura may happen.

So what exactly happens in the CSD phase?

As the CSD wave spreads in the cerebral cortex, the cells in the brain tissue release massive quantities of chemical messengers, including various substances that may influence pain perception. One hypothesis is that these so-called mediators diffuse from the tissue toward the meninges in the affected regions and trigger pain perception at nearby nerve endings. The nerves react in turn by secreting pro-inflammatory substances, resulting in neurogenic inflammation. Pro-nociceptive molecules also released in the process increase the pain duration and sensitivity.

Another research finding provides insight into blood flow in the brain and the associated issue of oxygen supply, which is particularly important in nerve tissue. Especially in migraine with aura, blood flow to individual brain areas is impaired during CSD. The poor blood flow means the brain is not getting enough oxygen. The resulting deficiency may in turn cause a migraine attack, creating a classic vicious cycle.

Migraine: still a major headache for scientists

Scientists have identified a very long list of processes potentially involved in migraine. The research described in this article is just a small part of the body of evidence. The real trick will be to piece all the separate research findings together into one big picture. Until that happens, a comprehensive concept that integrates and explains the neural processes underlying migraine will remain elusive. This coherent overarching concept should also provide a model for understanding migraine in its various different forms (with and without aura, for instance). Developing an integrated vision of a clinical entity that involves so many different factors is clearly a mammoth task for scientists. We promise to keep our readers up to speed on the latest research as the science evolves.