Migraine, once thought to be merely an excruciating headache, is now emerging as a far more complex condition, with new research offering hope for the estimated one billion people worldwide who suffer from it. A radical shift in our understanding of the disease, paired with advances in treatments, is changing the way the medical world views and addresses this debilitating condition.
Andrea West’s experience highlights the potential impact of new treatments. After enduring migraines for 70 years, West found relief in 2021 when she discovered gepants, a class of drug that promised to prevent attacks. When atogepant, a drug from the gepant family, was approved for use in the United Kingdom, West immediately consulted her doctor. Since then, she hasn’t had a single migraine. “It’s marvellous stuff. It’s genuinely changed my life,” she shares, a sentiment many migraine sufferers are now expressing after finding similar relief.
Historically, migraine was viewed as an unsolvable ailment, with ancient treatments such as attaching clay crocodiles to the head and drilling holes in the skull. By the 20th century, though more effective treatments were introduced, they remained ineffective for many, leaving millions of people to suffer in silence. Today, however, the landscape has drastically changed, largely due to breakthroughs in migraine research and treatment.
Medical professionals now consider migraine as a treatable and manageable condition, thanks to the work of researchers like Diana Krause, a neuropharmacologist at the University of California, Irvine. A greater understanding of the condition has led to developments in treatment options such as gepants, as well as monoclonal antibodies that block the calcitonin gene-related peptide (CGRP). These treatments have already been life-changing for some. However, many researchers are advocating for a broader, more nuanced understanding of migraine beyond the realm of pain alone.
Migraine isn’t merely a headache, but a condition that originates in the brain and can manifest in various debilitating symptoms, including light sensitivity, fatigue, brain fog, and nausea. Neurologist Richard Lipton from the Albert Einstein College of Medicine in New York City points out that migraine causes significant impairment long before the severe pain sets in. “I used to think that disability travels with pain, and it’s only when the pain gets severe that people are impaired,” Lipton explains. “That’s not only false, but we have treatments to do something about it.”
A radical shift in thinking about the brain’s role in migraine is also underway. The focus is now on understanding what triggers a migraine-prone brain to enter a hyperactive state, which ultimately leads to an attack. Researchers like Arne May, a neurologist at the University Medical Center Hamburg–Eppendorf in Germany, argue that to fully stop migraine, we need to understand how the entire system of migraine is activated, not just the pain itself.
For decades, migraine was attributed to either psychological or vascular causes, with theories ranging from stress-induced disorders to blood vessel dilation causing throbbing pain. However, new studies, particularly those involving brain scans, have painted a much more complex picture. The discovery that brain regions are activated during migraine attacks in the 1990s helped shift the perception of the condition as a neurological disease rather than a mere headache. May explains, “It was the very first time someone could point to migraine and say it’s a biological disease.”
Over the years, research has established that migraines consist of multiple stages, starting with a premonitory phase marked by symptoms like fatigue, nausea, and food cravings, which occurs hours or days before the attack. Then comes the headache phase, which often includes pain and other debilitating symptoms, followed by the postdrome phase, with effects such as depression or euphoria. In between attacks, some individuals experience a period of symptoms that may go unnoticed by others, referred to as the interictal phase.
The nature of migraine symptoms varies between individuals. For example, Dom Horton, a 53-year-old editor from the UK, experiences constant dizziness and mental fog without the associated headache. Meanwhile, Fiona Gartside, a 60-year-old veterinary surgeon in Scotland, deals with severe light sensitivity, nausea, and debilitating headaches that sometimes cause her to lose consciousness. While these symptoms differ, they share a common underlying cause: the brain’s hypersensitivity and the complex interplay of its regions.
The advent of gepant drugs and monoclonal antibodies represents a major step forward in migraine treatment. These drugs block CGRP, a protein that plays a key role in migraine attacks. Research led by Peter Goadsby, a neurologist at King’s College London, demonstrated that CGRP blockers were highly effective in alleviating headache pain and, in some cases, preventing attacks altogether. Goadsby says that patients who respond to these treatments often experience profound relief, with some expressing that they had forgotten what it felt like to live pain-free. “They’d forgotten before what normal was,” he says.
However, despite the success of CGRP blockers, there are significant limitations. These drugs don’t work for everyone, with some studies suggesting that only around 20% of people experience significant relief. Additionally, some symptoms, such as nausea, may persist even in patients who respond well to the drugs. West, for instance, still struggles with bouts of nausea despite the successful prevention of her migraines through atogepant.
This variability highlights a critical gap in our understanding of migraine. Goadsby argues that researchers need to explore alternative pathways and rethink their approach to the condition. “CGRP isn’t the only answer,” he stresses. Researchers are increasingly turning their attention to the brain’s hypothalamus, a key region involved in regulating emotional and sensory information, which may play a significant role in migraine. Studies suggest that the hypothalamus experiences increased connectivity with other brain regions just before a migraine begins, leading to a cascade of symptoms such as sensitivity to light and sound, cognitive impairment, and nausea.
The search for genetic and environmental factors that predispose individuals to migraines is also underway. Lyn Griffiths, a geneticist at Queensland University of Technology, points out that migraine has a heritability rate of 35-60%, and that genetic risk scores could help predict who might develop the condition. Additionally, researchers are exploring artificial intelligence (AI) to track potential triggers, such as sleep disturbances, hormonal changes, or weather patterns, which may help individuals predict and manage their migraine attacks more effectively.
Despite significant progress in the field, much work remains to be done. As migraine research moves forward, scientists are exploring not just the physical pain of migraines but the broader neurological and cognitive aspects that affect sufferers. A better understanding of the brain and its role in migraine could unlock new treatments, offering hope to the one billion people worldwide affected by this condition.
The above article is sourced from The Nature.
