Understanding headaches: medicine meets scientific research

One of the many benefits of being involved in the neuroscience world at Oxford is the opportunity to witness the convergence of science and medicine. The launch of the Oxford Headache Centre is a recent example of how scientific research can feed directly into medicine. This is a clinical department, for the treatment and care of those who suffer from chronic headaches; however, it also works directly with scientists on the cutting edge of migraine research. The aim of this multidisciplinary centre is simple; to convert the most recent research into better drugs for its patients as well as a greater understanding of the underlying causes of headaches.

Headache disorders place significant stress on not only the daily lives of the 90% of us who will face them at some point in our lifetime, but also on healthcare systems, with treatments costing up to £5 billion a year in the UK alone. But for such a huge prevalence rate, the burden that recurring headaches can have on daily life is still largely underestimated. Treatment options are available and can provide vast improvements to quality of life (for example, with the new NICE guidelines), but with limited awareness of these from both clinicians and patients, headache disorders still place a large pressure on the lives of those suffering.

Migraine is an extreme example of this. It is an old disease, with the earliest references to migraine dating back to ancient Egypt (2,000 BC). Primarily affecting women, migraine stems from an ancient Greek description of “half a head”, referring to the severe pain that patients experience to one side of their head. Topped off with nausea, vomiting, and intolerance to light, this disease is paralysing. What makes it a unique enigma for neuroscientists is that around 30% of sufferers experience blurred vision and see bright lights and shapes just before the pain begins. This is called an ‘aura’, a distressing warning that the migraine is about to start.

Migraine is believed by most modern neuroscientists to be caused by the nervous system; more specifically, a nervous system that is too responsive to pain. The aura experience is thought to be a wave of overexcitement that spreads across the neurons in the parts of the brain dedicated to vision, followed by a wave of very low activity. However, how the pain phase of the migraine then comes into play is unclear: is it caused by the brain, or instead by signals taken to the brain from elsewhere? The first migraine theoreticians discovered that the blood vessels in the brain became bigger and assumed that this was the cause of the pain. However, most modern researchers think that this is simply an after-effect of the pain. Instead, they look to the source of this network of blood vessels, to the base of the brain, where all the nerves from our body bundle up. The brainstem, one of the oldest parts of our brain, could be the source of all that pain.

Although the causes of migraine are still hotly debated, the picture is getting much clearer thanks to some important genetic discoveries in recent years. Some genes have been found to increase the risk of getting migraines, for example certain genes that have been linked to painful touch. A chemical in our brain called glutamate has also been implicated. Glutamate excites neurons in the brain, thus increasing their activity and communication, and a gene that controls when glutamate sends its signals to excite neurons is thought to be flawed in migraine sufferers. Perhaps most significant is recent migraine research on how an error in the gene that encodes a type of potassium channel (TWIK-related spinal cord potassium channel, or TRESK) could trigger migraines. This paper found that a genetic error meant that these channels, which normally carry potassium in and out of neurons, were not active enough. Importantly, this increased the risk of environmental stresses triggering pain centres in the brain – an unfortunate example of nature and nurture interacting. But this discovery does open a world of opportunities for treatment research; perhaps by increasing potassium transport in these TRESK channels, migraine pain could be treated.

The future of headache and migraine research seems to lie in our genes, and the next big discovery on the genetics of migraine may find a possible target for drugs and help to better understand what happens during migraine, from the aura to the pain. Despite migraine with aura making up only a small percentage of people who suffer with headaches, a better understanding of the condition could be translatable to other types of headache pain.

We are getting a better grasp on the causes of migraines and headaches in general, helped predominantly by the growing research on the molecular and cellular events taking place in the brains of people suffering from headache disorders. Current drugs and pain management plans are good, but with such a complicated and diverse pain as the headache, more is needed. Luckily, interest in headache research has risen remarkably in recent years, epitomized here at the new Oxford Headache Centre. Hopefully, thanks to the new stream of scientific research coming through its doors, the young doctors that will train at the centre will be able to transform cutting edge research into new and tailored treatments.