Peering into the Black Box of Migraine and Facial Pain

At the 2018 World Congress on Pain, headache researcher Arne May described progress in understanding migraine and facial pain. Image credit: olgamilagros/123RF Stock Photo.

Editor’s Note: At the 2018 World Congress on Pain in Boston, the biennial meeting of the International Association for the Study of Pain (IASP), researchers from around the world gathered from September 12-16 to discuss the latest pain research. Twelve young scientists attending the World Congress were selected to provide first-hand reporting from the event, as part of a science communications training program provided by the Pain Research Forum, RELIEF’s parent site. Here, Alexander Davies, PhD, a postdoctoral researcher in the Nuffield Department of Clinical Neurosciences at the University of Oxford, UK, reports on a plenary lecture delivered at the meeting by headache researcher Arne May; see related interview with May on the Pain Research Forum here. (RELIEF’s news coverage is editorially independent of its publisher, IASP. All editorial decisions about our reporting on IASP activities are made solely by the RELIEF editors).

A woman lies down in a quiet, darkened room with curtains drawn. Her head splitting with pain, she waits for the next wave of nausea to drag her from a bed she does not want to leave.

This scene, described by Arne May during his plenary talk at the 2018 World Congress on Pain in Boston, will be all-too-familiar to migraine sufferers, known as migraineurs.

Migraineurs may have attacks three or four times a month, with pain usually on one side of the head. In about 30% of cases the migraine will be accompanied by an “aura”, a sensory phenomenon that is usually visual. But why does migraine pain occur only in the head?

When May, a professor of neurology and headache specialist at the University of Hamburg in Germany, started out in his career as a neurologist in 1991, migraineurs were “between a rock and a hard place,” he said. More common in women than men, migraine had for years been considered a psychological disease, seen as a “black box” by doctors who had no specific treatments to offer their patients.

Fortunately, we now know much more about migraine. Researchers have discovered that it has specific neurobiological underpinnings, featuring changes in brain activity along with other alterations of the nervous system. During his talk, May discussed the neurobiological basis of migraine, and also the relationship between migraine and facial pain, the latter being the black box that migraine once was.

What happens in the brain before a migraine?
Interestingly, May’s research has shown that there are changes in brain activity in migraineurs even before they suffer a migraine attack.

In one of May’s studies, a patient with very regular migraine attacks (two to three per month) underwent a functional magnetic resonance imaging (fMRI) brain scan every day for 30 days, always in the morning. Because the timing of migraine attacks is difficult to predict, this strategy maximized the chance of catching a migraine attack on the day it occurred. When brain activity during an attack was recorded, May and his research team could then compare it to brain activity on the days before the attack (known as the “pre-ictal” phase) and after the attack (the “post-ictal” phase).

During a migraine attack a region at the base of the brain called the brainstem becomes active. What May saw the day before an attack, however, was activity in a region of the brain called the hypothalamus, which controls basic functions like body temperature, appetite and daily hormone changes.

May acknowledges that having a migraine attack, and vomiting—another symptom of migraine—in an fMRI scanner was not a pleasant experience for his patient! So he remains extremely grateful to the participant in his study, which, for the first time, showed that brain activity changes not just during a migraine attack, but before it too.

One nerve with three branches makes for a complicated relationship between migraine and facial pain
Thirty years ago there were no specific treatments for migraine other than the fungal extract ergotamine; sometimes the usual painkillers simply don’t work. Now, patients have access to triptans, a class of effective medications for migraine and cluster headache (a condition characterized by bouts of severe headaches on one side of the head) that have no effect on other types of pain.

Triptans work by mimicking the activity of serotonin, a neurotransmitter, on the trigeminal nerve. This is a cranial nerve (that is, a nerve that emerges directly from the brain) with three main branches in the head and the face. In particular, triptans act upon the 1st nerve branch, which goes to the head and is connected to the blood vessels and membranes surrounding the brain.

Pain that involves the trigeminal system has a strikingly peculiar and prominent characteristic that sets it apart from other kinds of pain that people experience. The head is the only body part where regular attacks of specific length can occur without any external cause. Indeed, migraine pain will arise from a period of quiescence such that sufferers may struggle to pinpoint exactly when it began, and it can also be accompanied by symptoms such as teary eyes, skin flushes and palpitations. Yet it seems that this is restricted to the 1st trigeminal nerve branch, as regular, periodic attacks of pain are not reported from the face.

This got May thinking: Why is it only the 1st branch of the trigeminal nerve (also known as the “ophthalmic” branch) that seems to be affected during migraine? Why not the 2nd (“maxillary”) and 3rd (“mandibular”) branches, which go to the face, as well as the teeth? Because all three branches of the trigeminal nerve originate from the brainstem, and migraine affects the brainstem, it would seem that all three branches of the nerve would come into play during a migraine, leading to broader pain in the head and face, but this is not the case. So May went back to his patient records to take a closer look.

He realized that there are a small number of migraine patients who do indeed suffer attacks of facial pain, usually on one side of the face, although these patients are extremely rare. There may be more cases of “facial migraine” but, because there is no agreed-upon classification of this condition, it may be missed the migraine specialist.

Perhaps there really is something unique about the 1st branch of the trigeminal nerve? May acknowledged that connections from the first branch to the blood vessels of the brain probably play a role in migraine pain, and these connections are absent from the 2nd and 3rd branches. However, the dilation of blood vessels that is sometimes seen during a migraine attack is likely to be a consequence and not a cause of the migraine, so it may not explain all the differences between migraine and facial pain.

Regardless, May suggested that if chronic facial pain patients came to the headache or migraine clinic, the doctor might be better placed to offer diagnosis and specific medication owing to the potential similarities in the conditions. Instead, facial pain patients may see their general practitioner, who may fail to make a sufficient diagnosis, before visiting an ophthalmologist and then a dentist, passing from one specialist to another. As a consequence, in the course of their treatment these patients may have new glasses fitted, or even have teeth removed.

May believes this is all because chronic facial pain is currently the black box that migraine once was. With no other diagnosis available, doctors consider facial pain a psychological condition, just as they thought of migraine 30 years ago, or offer invasive procedures to patients, like root canal or tooth extraction, that may do little to address the underlying cause of their pain. When a dental treatment fails to relieve the pain the patient is left with no option but to begin the cycle of again going from doctor to doctor in search of a diagnosis. In some cases the patient may end up with no teeth at all!

How to break this cycle? May’s view is that better communication is needed between dentists, neurologists, physiotherapists and orthopaedic specialists, as well as researchers. “Now is the right time to join forces,” he urged.

The way forward
While triptans are effective at alleviating migraine pain these drugs are not a cure. More evidence is needed to determine if triptans work for facial pain too. Many people with migraine or chronic facial pain deal with these conditions for their entire lives. So more research is required to understand what causes the changes underlying the generation of migraine and facial pain in the first place.

The fact that there are multiple forms of headache and facial pain also suggests that the other branches of the trigeminal nerve, as well as cranial nerves that enter the neck, may drive pain in different ways. The black box needs to be prised open further.

May identified the international acceptance of a definition of migraine as one of the key moments that changed the lives of migraine patients. This is because patients could now receive a diagnosis and appropriate treatment from their doctor faster and more effectively than before.

An equivalent international classification for facial pain will soon be published, and May is hopeful that this may kick-start a better understanding of the causes of this condition, which could lead to new treatments in the way it did with migraine.

“The ultimate winner will be our patients,” he said.

Alexander Davies, PhD, is a postdoctoral researcher in the Nuffield Department of Clinical Neurosciences at the University of Oxford, UK.