By Tom Zeller Jr.
Mr. Zeller is the editor in chief of the digital science magazine “Undark.” A former reporter for The New York Times, he is working on a book about headaches.
I have headaches. Not the low-grade, annoying, “I’ve got a headache” sort of headaches. I get those, too. Most everyone does, and they are a drag.
No, when I say that I get headaches, I mean that at intervals that are largely unpredictable, a knot of pain rises deep inside my head, invariably sensed behind my right eyeball. It then swiftly clicks up through the intensity scale, racing past that dull ache you might get from staring at the screen too long, leapfrogging over that doozy you had the morning after your brother’s wedding, skipping past the agonizing-but-fleeting stab of an ice-cream headache, and arriving, within a matter of minutes, at a pain so piercing and sustained that I can only grip something sturdy, rock back and forth, and grunt until it subsides.
Mine are what doctors call one of the “primary headaches” — recurring and often excruciating disorders that are not byproducts of another condition (or self-inflicted by last night’s cocktails), but relentless, and in many ways still poorly understood disorders unto themselves. We know them by common names like migraine, which affects tens of millions of Americans, disproportionately women. I suffer from another flavor known as cluster headaches (technically a trigeminal autonomic cephalalgia). And there are others, with myriad and imperfectly drawn lines distinguishing them.
If you experience migraines or cluster headaches — and research suggests that more than a billion people worldwide do — you probably know something about shuttling from doctor to doctor looking for someone who “gets it.” You know what it’s like to gladly gobble up pills that don’t really work and that leave you miserable in other ways. And you might even know the same sort of incredulous exasperation that has driven me to wonder, from my fetal position on the bathroom floor: “How is it possible that science can’t fix a damn headache?”
I won’t go so far as to say we’re anywhere near a fix. In many ways, we’re farther from understanding these disorders than we ought to be, given the billions of dollars they extract in health care costs, and the outsize toll they take on people — usually during what ought to be their most productive and creative years. But I can also say with some confidence: There’s probably never been a better time to have a headache.
In March, one of the most coveted prizes in neuroscience, the $1.5 million Brain Prize, went to four scientists who, often working independently of one another and beginning roughly in the 1980s, set about revolutionizing our understanding of migraines and similar headaches. Their work and that of many others has been slow but steady, overturning long-prevailing and facile notions like “the migraine personality” (a derisive category primarily aimed at women), or the idea that stress and a weak constitution were the cause.
They’re not. Rather, primary headaches are true neurobiological disorders and I know this because on a sunny day last spring, and after a few weeks of imperfectly managing excruciating pain with lousy drugs and haggling with doctors and insurance carriers, I stood in my kitchen, hiked down my trousers, and administered into my bottom three (still very expensive) injections of a new elixir — a monoclonal antibody designed to inhibit a neuropeptide called CGRP, short for calcitonin gene-related peptide.
CGRP, discovered only in the 1980s, is a key component in the nervous system’s head pain pathway and appears to be intimately involved in the generation of migraines and clusters. Scientists now believe these headaches arise in part when cerebral structures linked to head pain signaling become hyperactive — a sort of neurovascular communication gone awry. And while the brain itself does not feel pain, it can respond to this errant activity by sending severe sensations of pain to parts of the head that can — quite likely the membranous layers of tissue between the skull and the brain called the meninges. When this happens, patients can also experience increased sensitivity to light, sound and smell, as well as nausea and even vomiting. This can continue unabated for hours, and sometimes days, for some people living with migraine.
This new class of medication, the first of which was brought to market by Amgen and Novartis and collectively called CGRP inhibitors, is changing the lives of many headache patients, and it is no exaggeration to say that a direct line can be drawn between the research honored with the Brain Prize and events in my kitchen that day last spring. Can I say unequivocally that it worked for me? Maybe. I think so. My headaches abated shortly after — though it’s characteristic of clusters to go into periods of remission anyway, only to reappear.
But even if it did work — and welcome as these advances are — any neurologist working today will readily admit that we remain in the Stone Age with regard to many aspects of these most common and debilitating disorders. That is probably the result, at least in part, to historical biases. As Joanna Kempner, an associate professor of sociology at Rutgers University, nimbly laid out in her 2014 book “Not Tonight: Migraine and the Politics of Gender and Health,” migraine headaches in particular have been given inadequate consideration by the medical and scientific establishments. This dismissal, Dr. Kempner argues, was at least partly tied to the fact that migraines surface more often in women, whose physical pain was often ascribed a psychological or emotional origin. And while those diagnoses have now mostly been discarded by the medical establishment, she suggests that gender biases in headache treatment have not.
To be sure, our brains are unfathomably complex organs, and they are difficult to study. But the dynamics that Dr. Kempner identifies almost certainly helped to prolong scientific ignorance of headache mechanics and treatment for decades, and for everyone. Consider, after all, that the Amgen/Novartis antibody was the first drug ever approved in the United States to specifically prevent migraines. The first — and that was a mere three years ago. (Side effects so far generally appear uncommon and mild, though the long-term picture remains to be seen.) Eli Lilly secured approval for its version of a CGRP inhibitor to treat cluster headaches only in 2019, and new classes of CGRP drugs are still emerging. But since the dawn of drug regulation, every other pharmacological dollop aimed at preventing these diabolical headaches — a menagerie of beta blockers, anti-epileptics, anti-depressants and other drugs — were researched, developed and designed for other diseases. They simply seemed to help some people with headaches as a side effect, and so doctors just gave them a go.
In my work as a journalist exploring the modern evolution in headache science, I’ve spoken to many patients who suggested that ignorance, both clinical and cultural, persists. As with so many other pain disorders, Black patients are far less likely to have their head pain properly diagnosed than their white counterparts. And while the World Health Organization places headaches among the leading causes of disability and lost productivity on the planet, our knowledge of headaches, like that of so many other diseases, skews toward the rich world, leaving incidence and impact in the developing world vastly understudied.
At the same time, the new drugs, while remarkably effective for some people, are yet another heartbreaking failure for others, suggesting that a more fundamental neural trigger or target remains elusive. These medications are also not cures, and many patients must continue to take them periodically — even though they can cost more than $600 for a single injection. Many headache sufferers are finding that their insurers will refuse to cover them.
For all the recent progress, funding from the National Institutes of Health for basic research into headache disorders remains incommensurate with their enormous social costs, and far too few young doctors see headache specialization as fertile ground for a career. One young medical student with an interest in neurology told me she was taken aback that her studies focused so heavily on unusual brain disorders, given that headaches are so common — and still so mysterious. “We got so much teaching about other things, which are important too, but way less common,” she said. “I was surprised by that.”
Look, I get it. In a world troubled by all manner of disease and unrest, it can seem absurd to complain about headaches. But this, too, is what makes the path of a chronic headache sufferer — or really anyone with any sort of chronic pain — a uniquely lonely one. The pain won’t kill us, sure, but we can receive prolonged physical beatings, without explanation, at any moment — a merciless cycle that some studies have shown can increase suicide risk. Some headaches are even thought to be capable of administering one of the most extraordinary sensations of pain known to the human body, but they occur in a location that makes them entirely invisible to puzzled onlookers (and for most of history, to scientists, too). And all such pain bears a name — “headache” — so common, so boring and so utterly diluted by its resonance with other, lesser things, that sufferers are often too ashamed to even mention it.
But ask any people who suffer from migraines or similar headaches about the months spent being dismissed or misdiagnosed by unenlightened doctors, or the years spent swallowing or inhaling or injecting hand-me-down, off-label drugs that make them sleepy or stupid, that embrittle their bones or race their hearts, or present a litany of other side effects. They are in your family. Or you work with them. No, they won’t die. But they are very often experiencing inscrutable, exhausting bouts of pain — or living in fear that it’s just around the corner, again.
“The most painful thing to me, aside from my physical pain, is the incredible feeling of loss migraines have brought me,” a young headache patient, just 22 at the time, told me. “I know I am smart, but my schoolwork does not mirror it. I know I am social, a good daughter, a good friend, but I worry my life does not mirror this either,” she said. “I guess the loss I feel is the loss of what I could have been, or could be, or could do, without migraines.”
In March, patients and advocates for headache science once again made an annual appeal to Congress for additional funding for research and other headache treatment initiatives. The yearly Migraine World Summit offers patients and practitioners around the globe online access to experts working at the bleeding edge of research. Headache research centers are busy studying these disorders from Texas to Denmark, there’s a growing market potential in still newer drugs, and clinical trials for other potential therapies — from psilocybin to vitamin D — are in the works.
This upswing in therapeutic interest in headaches is exhilarating and full of anticipation, and the swashbuckling science being done is extraordinary. It really is a fine time to have a headache. But it’s also disheartening that a condition that brings such regular anguish to so many people remains so mysterious — and so undertreated.
Tom Zeller Jr. (@tomzellerjr), a former reporter for The New York Times, is the editor in chief of the digital science magazine Undark. He is working on a book about headaches.