The mystery of migraines

The mystery of migraines

According to the NHS, around 10 million people aged 15 to 69 in the UK suffer from migraines. But our understanding of them is still incomplete, and there isn’t even a pill to make them go away.

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Published: October 15, 2022 at 9:00 am

Why do people get migraines? It’s a simple question, but one with an incredibly complicated answer. If ‘answer’ is even the right word. Because, in truth, as far as the science is concerned, the most honest and straightforward answer to ‘why do people get migraines?’ would be ‘we don’t know’. Despite countless years of research and study, it seems that the underlying science of migraines is so nuanced and complex that our understanding is still far from complete.

However, it’s always worth emphasising that ‘incomplete understanding’ is a far cry from ‘zero understanding’. Science has revealed many significant things about migraines, why they occur, why they endure, who they affect, and why they hit us so severely.

Is a migraine just a bad headache?

For those lucky enough to not have to deal with them, it’s easy to label migraines as a type of headache. However, while ‘headache’ is an undeniable aspect of the experience of a migraine, migraines are actually much more than just a headache, and have numerous key differences.

For one, headaches are more common than migraines. Estimates suggest that 75 per cent of all people will have experienced at least one headache within the last year. By contrast, evidence suggests that just under 15 per cent of people experience migraines, with less than 10 per cent of those having chronic migraines.

There’s also a much clearer gender divide with migraines, with between two to three times as many women enduring them as men (a ratio that fluctuates depending on stage of life).

Also, while there is uncertainty and overlap, headaches and migraines have distinct features. The more common types of headache are tension headaches (the feeling of pressure or tension on both sides of the head), sinus headaches (the result of congestion, where the sinus passages swell and put pressure on tissues behind and around the eyes and nose, causing pain), and cluster headaches (painful, repeating headaches, often localised to around the eye regions on one side of the head).

While these headaches can be misdiagnosed as migraines, and vice versa, migraines typically have their own unique features that set them apart. They tend to be much more debilitating, with increased fatigue and sensitivity to light. They also last longer (and have a bizarrely reliable form of progression, with distinct stages), and include nausea and, in many cases, sensory distortions, like the perception of ‘auras’.

Ultimately, while there is undeniably a lot of overlap, migraines have a different mechanism and expression compared to most headaches, to the extent that they’re officially recognised as a neurological disorder, where headaches usually aren’t.

The root cause of migraines

The fact that we’re still unsure about how and why migraines happen seems even more surprising when you consider how long we have been dealing with them. Texts from Ancient Egyptians and Greeks, dating as far back as 1200 BC, describe specific ailments and experiences that are indicative of migraines.

Among the many complicated processes we now know are taking place in the head and brain when a migraine occurs, if there’s one that’s likely to be at the root of them all, it’s what’s known as cortical spreading depression, or CSD.

CSD is when a neuron (a brain cell) experiences a sudden burst of activity, known as depolarisation, a brief ‘flipping’ of the microscopic voltage that exists along the cell membrane of all neurons. This depolarisation is the basis of all the activity and signals that occur within our brain and body. However, it’s a demanding process, so after it occurs, neurons are briefly ‘depressed’, or in a resting state, where they aren’t as active as normal.

Depolarisation is typically initiated and sustained as part of one of the countless processes occurring within the human brain. However, it seems that sometimes, for whatever reason, certain neurons will depolarise… just because.

Presumably because all neurons are interconnected, and all their activity ultimately boils down to changes in the concentrations of chemicals in and around them, this unexpected depolarisation ‘spreads’ to neighbouring neurons, and on to the next ones, and so forth. This process is incredibly slow and can take many minutes, hours even, to travel from one part of the brain to the next. And so, we have CSD.

Unfortunately, anomalous neurological activity in important and delicate brain regions can lead to negative consequences. It’s likely that this spreading wave of neurological activity is what causes the unpleasant aspects of migraines, and would explain why migraines have such distinct stages.

The wave of CSD begins in one part of the brain, causing one suite of symptoms, and travels along established routes, incorporating more brain regions, and thus causing different (and often more severe) symptoms along the way. Indeed, if the CSD spreads as far as the occipital lobe and visual cortex, you would expect to see visual symptoms, which would explain why some migraines have auras. It would also explain why migraines last so long. The triggering wave of CSD slowly travels through the brain, prolonging the suffering of the migraine victim.

© Scott Balmer

Nerves vs blood vessels

It’s all well and good saying that migraines are due to a slow-spreading wave of anomalous neurological activity in the brain, but how do we get from something so ‘fundamental’ to something as tangible as severe headache pain, nausea, light sensitivity, and all the rest?

That’s where the issue becomes trickier. For some time there was a notable debate as to whether the main aspects of migraines were neurological (due to unhelpful activity in and between brain cells) or vascular (due to changes in the blood vessels that supply the brain).

For many years, it was assumed that migraines were more vascular in nature. The throbbing nature of many migraines can be reminiscent of the feeling of your pulse, and suggests tangible changes in pressure, which would obviously point towards an issue with the brain and head’s blood supply.

It was thought by many that the blood vessels in the tissue layers that surround and protect the brain underwent vasodilation (expansion), which caused an increase in pressure in the already densely crowded environs of brain tissue, and this pressure increase was perceived as pain. But more recent evidence suggests that vasodilation isn’t as prominent a factor in migraines as was previously assumed.

However, lately many have leaned towards a more neurological mechanism when explaining migraines. After all, if it stems from waves of unhelpful activity in neurons, this is bound to have knock-on effects in other neurons, right?

A particular focus for the neurological aspects of migraines is the trigeminal nerve. One of the 12 cranial nerves – the large nerves that connect the brain to the face, neck and torso – the trigeminal nerve is a triple-branched nerve that conveys, among other things, the sense of pain from the face and head, hence the chronic pain of trigeminal neuralgia.

Correspondingly, abnormal activity in the trigeminal nerve is closely linked to the symptoms of migraine, and helps explain why grinding your teeth or clenching your jaw (two actions that depend on the trigeminal nerve) are associated with triggering migraines.

In truth, though, it’s extremely unlikely that migraines are exclusively caused by neurological or vascular factors. For instance, some argue that CSD causes vasodilation in the trigeminal nerve, which leads to increased pressure, and therefore pain. This means it’s both a neurological and vascular issue, hence some people referring to migraines as a neurovascular condition.

Indeed, at this level, you could argue that differentiating between neurological and vascular aspects is tricky, and ultimately meaningless. Activity in neurons regularly leads to changes in the properties and behaviour of nearby blood vessels, and blood vessels directly affect neurons via the pressure and chemicals they apply. This means that the anomalous activity in the brain would very likely be affecting both nerves and blood vessels at the same time.

Read more about migraines and headaches:

Migraines, chemicals, hormones and sex

Thus far, it seems like migraines are the result of waves of anomalous nervous activity, spreading slowly throughout certain areas of the brain. This leads to unhelpful and disruptive changes in the neurons and blood vessels in those areas, which in turn cause the impressively varied – if deeply unpleasant – symptoms of migraine. It makes logical sense that if you induce anomalous activity in several important and fundamental areas of the brain, it’s inevitably going to lead to a wide range of physical problems and disruption.

But it’s possible to look even deeper than we already have. Even if we accept that migraines arise because of abnormal neural activity that leads to CSD (although another theory points to abnormal activity in the brainstem), what is it that causes this unusual activity in the first place?

As ever, it’s hard to be 100 per cent sure, but a lot of data points to it being, at least in part, the result of a drop in the levels of vital neurological chemicals in the relevant brain regions.

One of those is our old friend serotonin, a neurotransmitter with many important roles, most famously in the regulation of mood. However, there’s a lot of research that points to drops in serotonin levels being a potential trigger for the onset of migraines. Supporting this is evidence of a link between migraines and major depressive disorder.

But serotonin isn’t the only crucial brain chemical that can lead to migraines when the levels of it drop. Another one is oestrogen. And oestrogen is a hormone that has a far more prominent role in female biology than male. This would explain why women are far more prone to migraines than men, and how their reproductive cycle and stage of life can play a big part in their experience of migraines.

One possibility is that the presence of serotonin and/or oestrogen stabilises the activity in key neurons, so when one or both is depleted past a certain point, the neurons depolarise ‘randomly’, and we get CSD. And therefore migraines.

Other chemicals play a role too. Stress is regularly cited as a common cause of migraines. Among other things, cortisol (a chemical released during stress) is known to make neurons more sensitive to pain, so severe or prolonged stress could be what tips those vulnerable to migraines into the onset of an attack.

And of course, if stress is a factor in causing migraines, then being regularly incapacitated by migraines is undeniably stressful. So, a vicious feedback loop kicks in.

© Scott Balmer

Can we treat migraines?

Because migraines are such a debilitating and enduring problem, it’s hardly surprising that there is a great deal of interest in anything that could cure or treat them, or even just provide some relief from the symptoms. As a result, there are a wide range of potential treatments and interventions for migraines. Although some seem rather more credible than others…

Everyday painkillers

The most typical means of tackling a migraine are common over-the-counter analgesics like aspirin, ibuprofen and paracetamol. These can often provide some modicum of relief from migraine symptoms, albeit to a rather limited extent. Interestingly, exactly how they work on migraines remains unclear. But then, we’re still not sure exactly how paracetamol works either. We just know that it does.

Triptans

Triptans are an increasingly common go-to for treating migraines. They do not prevent migraines; they are taken once symptoms start. They work on the serotonin neurons (which we now know are key to the migraine process) and block pain pathways in the brain, therefore neutralising the painful migraine headache. They have many potential side effects, and don’t do much for the nausea, fatigue, or sensory aspects. But it’s better than nothing.

Botox

Unless your migraine is caused by stress over how many wrinkles you’ve got, most wouldn’t consider Botox a potential migraine treatment. But evidence suggests otherwise. Botox is a substance that paralyses nerves, and when administered for migraines, it’s injected under the skin or into the muscles around the forehead, ears and neck. Not the most orthodox solution maybe, but something that could bring a smile back to your face.

Surgery

As a last resort, surgery can be used to ease migraines. Nerve decompression surgery, a technique pioneered by plastic surgeons, surgically alters, or relieves pressure on, the nerves responsible for migraine pain in certain patients, thus treating the condition.

As ever, there are risks with any surgery, so it depends on whether the migraine is so bad that submitting to a procedure which involves ‘nerves’ and ‘scalpels’ seems like the better option.

Migraine-relieving hand clips

Every part of the body is connected to the other via our nervous system, so I would never say that migraine-relieving hand clips are just small bits of inert plastic that have no feasible mechanism of dealing with a migraine. But I’m thinking it pretty hard.

Migrainerelief cap

The premise of migraine relief caps seems to be that putting something on the head, maybe something that covers the eyes to reduce sensory input, will make a migraine better. If nothing else, the embarrassment of being seen wearing one may distract from painful migraine symptoms.

Read more about headaches:

©Wang and Pan et al