“I’ve never felt a pain like that at any other time,” says Tom Zeller. “I liken it to having your hand on a hot burner and not being able to take it off. It’s that level of intensity, that you must move. You’re highly agitated. You sometimes bang your head
on things because the pain is that bad.”
The former New York Times journalist and author is describing the experience of a cluster headache, a rare form of headache causing pain so severe it’s been described as the “suicide headache”. In his book The Headache: The Science of a Most Confounding Affliction – and a Search for Relief, Zeller documents his own and others’ experience of debilitating pain from migraines and cluster headaches – collectively known as headache disorders – and the science behind the pain.
For something that’s thought to affect one in seven people, surprisingly little is known for certain about why these headaches happen. As Zeller writes, science can’t even really agree on what is hurting.
Asked if he can say for sure what a headache actually is – having researched and written a whole book on the subject – Zeller tells the Listener with a laugh: “I would say the short answer is no. Assuming we’re talking about primary headache disorder, like a migraine or a cluster headache … the top headache scientists in the US told me we know very little.
“We know some things, but it’s not very much. We know there are certain chemicals that are expressed when a headache is happening. We don’t know all of them, but we know some of them. We know that certain parts of the brain are lighting up during that pain event. And with migraine in particular, that there are associated neurological symptoms that can come hours or even days before. So there’s definitely a central nervous system activation going on.”
Beyond that, the experts can’t really even say which anatomical structures are hurting. “We can’t locate the pain in any particular place. It might in fact be nowhere at all.”
Root cause
Two competing theories have prevailed when it comes to headache pain over the years: that they are a vascular issue affecting the blood flow in the head, and that they are a central nervous system issue.
In most primary headache disorders, says Zeller, the pain is unilateral: almost always on one side of the head. “And that’s also a clear sign, if you think about it for even a minute, that the central nervous system is involved.”
If headaches were vascular, he points out, since the vasculature is everywhere, you’d expect the pain to be all around the head. The vascular theory is out of favour now, though not all headache scientists are ready to completely dismiss it.
For decades, it was assumed the brain itself was insensate – unable to feel pain, he says. There’s some debate about this now.
“But we used to think if the brain is mostly insensate, then surely it has to be some structure in the head that can feel pain. And really the only thing would be the meninges – the [membrane layers] that wrap around the brain. But so many experiments have been conducted that suggest it can’t possibly be true. It’s this really confounding thing where there are all these competing theories, but there’s also always at least one study and often multiple that just completely refute one theory or another.”
He cites the example of the trigeminal nerve; the nerve that provides communication for sensation in the head and face.
“It seems almost certain that the trigeminal nerve is involved in some way in the transmission of these pain signals in both migraine and cluster headache. The assumption was for decades that this nerve must be the conduit that’s moving these signals or creating this pain alarm. And so if you could – in a worst-case scenario – sever that link, you’d cure the headache. But here is a study in which a guy with relentless cluster headaches, not responding to anything at all, has the trigeminal connection severed and still gets the headaches. So again, it’s almost back to the drawing board on every front.”
As for the root cause of the pain, the prime suspect is an abnormality in the hypothalamus, the brain’s “master clock” that governs circadian rhythms and regulates body temperature. Clusters often arrive at specific times of year – particularly as temperatures rise or fall in spring or autumn – and occur at or near the same times of day or night – hence the name.
Zeller writes: “One of the telltale signs of a cluster attack, aside from the frantic behaviour of the patient, is a suite of accompanying symptoms arising from activation of the autonomic nervous system, which is not under voluntary control. These include ptosis, or the drooping of the eyelid; miosis, or pronounced constriction of the pupil; lacrimation, or excessive tear production; nasal congestion and runniness; facial sweating; and even perceptible swelling around the eye.”
He says although scientists still don’t know precisely how the hypothalamus is involved, brain scans of sufferers consistently show activation of the hypothalamus during cluster headache episodes.
For some, however, the pain attacks are chronic – occurring at any time of year. Genetic factors may also play a role.
Most headache sufferers report a similar frustrating experience: a process of years to get taken seriously and diagnosed followed by years to find a treatment that works. Photo / Getty Images
Inescapable pain
What is known for sure about headache disorders is that the pain is very real for sufferers. Zeller describes his harrowing experiences from his 20s onwards of debilitating and unpredictable pain, and the often-fruitless search for relief with treatments ranging from heavy pharmaceuticals to hallucinogens.
He speaks to other migraine sufferers (known as migraineurs) and those struck down by cluster headaches (which affect an estimated 6000 New Zealanders). Most report a similar frustrating experience: a process of years to get taken seriously and diagnosed followed by years to find a treatment that works. Often, sufferers will find something that gives relief only for the effects to wane over time, putting them back where they started. They can never be secure in their lack of pain.
“A lot of times I heard it described to me as this sort of drag on life,” Zeller says. “You can never kind of fully take flight, because you’re either managing some fairly miserable side effects from the drugs you’re taking, or, when you’re better and not feeling pain, you have this sort of low-level dread because you know it’s going to come back at some point.”
That’s been Zeller’s own experience, despite his success as a reporter and more recently editor of online science magazine Undark. “I’ve had a good career and I’ve managed to write a book even through all of this, but I also think that like a lot of headache patients I talk to in the book, you are always going to wonder what you might have done had you not had this thing grabbing your ankle and holding you down all the time. I would be lying if I said it didn’t affect my work. I definitely would sort of rise to opportunities as they came and then shrink from them when the headaches came.”
We all have headaches; they’re ordinary. This is a category difference.
The 56-year-old describes not wanting to explain his headaches at work or to identify himself as a headache sufferer. “It definitely kept me at the periphery of things in a way that might not have been the case if I hadn’t had them.”
Headache disorders are often misunderstood – and trivialised – by those lucky enough not to suffer with them. Zeller thinks this is part of the reason for the hiding.
“I think a lot of it has to do with the language we use to talk about headache disorders. I mean, the same word we use to metaphorically describe our taxes or sitting in traffic – these are all headaches, right? And we also use that same word to talk about a condition that we all experience from maybe a skipped lunch or maybe we had too many cocktails the night before. We all have headaches; they’re ordinary. But this is a category difference. And yet we often have to use the same word.
“Headache sufferers learn to internalise or at least to not talk about it too much because it does feel like, well, it’s a headache, right? How bad could it possibly be? Surely – and I think women experience this far more than men, particularly because they present with migraines so much more often than men – the implication is, if the headache is laying you low, then perhaps you’re a wee bit dramatic or maybe overly sensitive.”
about one in 1000 people suffer cluster headaches, which are more prevalent in men. Photo / Getty Images
Battling bias
That migraine in particular has long been regarded as a “women’s disease” may account for some of the mystery surrounding it, as well as the lack of interest over the years from the scientific community in delving into headache disorders more. Migraine is two to three times more common in women, according to the Migraine Foundation Aotearoa New Zealand, which estimates more than 750,000 Kiwis suffer from them.
Globally, about 15% of the population is estimated to suffer migraines, whereas about one in 1000 people suffer cluster headaches, which are more prevalent in men.
“As with a lot of things in women’s health, these [migraine] conditions get trivialised,” Zeller says. “And I think this is true for disorders that have a mysterious, misunderstood origin, particularly central nervous system disorders that don’t have a clean biomarker or don’t have an indication of an injury. There is a tendency to think maybe it’s all in your head. Maybe you just need to relax a little bit more.”
Zeller writes of promising young neuroscientists being actively discouraged from embarking on studying headaches. “I have to tell you, every neuroscientist and neurologist I spoke to who does study headaches has heard the same thing. Like, why are you doing that? That’s just for the second-rate researchers. Why don’t you study something more important?”
This attitude fuels a self-perpetuating cycle where headache research doesn’t attract funding – researchers, when picking a discipline, pay heed to where funding is going, and it frequently goes to other, “sexier” diseases.
New frontiers
Things may be changing, however. Recent drug discoveries have brought relief to many migraine sufferers and become, if not blockbuster medications, at least profitable avenues for research. In 2018, the first preventive drug in 60 years designed specifically for migraines was approved in the US. Known as a CGRP blocker, it targets a particular neuropeptide that signals pain and has a preventive effect.
“Up until that point, every other [preventive] drug that was given to a migraineur going into the clinic – and the same with cluster headache – was a drug that was developed for some other disorder. Maybe it was depression, maybe it was an anti-epileptic; it runs the gamut. And they had nasty side effects, but some anecdotal clinical evidence suggested that it kind of helped some people with headaches, so they would prescribe it,” says Zeller. “This was the sad tableau that most headache sufferers wandered through hopelessly up until 2018.”
CGRP blockers, however, remain unavailable on prescription in New Zealand. The clinical body that advises drug-funding agency Pharmac has, since 2023, recommended it fund three CGRP blockers and last month added a fourth to the list. To buy unfunded, an individual injection ranges from $300 to more than $1000.
Pharmac says all four types are treatments it would “like to fund when budget allows” but it cannot say when this will be. “It depends on whether Pharmac has the budget available, the success of negotiations with suppliers, the available clinical evidence about the benefits of the treatments, and how we’ve prioritised these medicines compared to others we would like to fund.”
For patients for whom CGRP blockers work, it can be almost miraculous. Illustration / Getty Images
Effectiveness may wane
The drugs work very well for some people – roughly half of those who try them. Zeller credits them with helping with his cluster headaches, too. “I think what makes them unusual is that for those patients for whom it does work – and we all have different genetics and we all have different physiologies, so it’s hard to know for whom these things are going to work – it can be almost miraculous. People who have had migraines their whole lives, with just one treatment with these injections are awakening … they’re back out into life and they can do family, and they can work in ways that they haven’t for decades.”
However, he says, it’s emerging that even CGRP drugs may lose their effectiveness over time – a common scenario for headache sufferers. “It’s the natural course of things. Our bodies are very plastic, and there’s a certain adaptability to drugs. And our hormones are constantly changing. Our metabolisms are constantly changing. Our livers become more adept at dispensing with the chemicals that we introduce. It’s not unusual that this would start to happen with CGRP drugs, too. But it is one of the things that really makes it very frustrating for a chronic pain condition like this.”
Zeller says women, especially, can be made to feel they’re drug-seeking when they ask for help as the drugs’ effects start to wane. “They get the feeling either overtly or implied that … maybe it’s you and not the drugs.”
The new frontier in headache research includes exploring the gut-brain axis, the known connection between the two organs, and in another stream, the potential of psilocybin (magic mushrooms) to help with cluster headaches. The online community who call themselves Cluster Busters – members share their personalised magic mushroom formulas – have inspired researchers to take a closer look. Zeller, too, has self-experimented with mushrooms. “I tried to do it. I just got high. It didn’t really stop my headaches. But you know, any port in a storm, as they say.”
He says his own headaches have become less frequent – something that happens with age in cluster headache sufferers. “I’m definitely in a better place than I was through most of my 20s and 30s, which was just a frantic, drug-addled gauntlet.”
And he offers hope for anyone who suffers migraines as well. “You’re not alone, even though it can often feel like that. There are probably a billion migraine sufferers alone on planet Earth. So you’re in good company.
“That’s cold comfort, I think, when you’re going through the pain. But if there’s anything you can take comfort in, it’s that science is finally starting to pay attention to these things and that real relief for many people is already starting to become available. And I think more of it is on the horizon. So, hang in there.”
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