Migraine is a recurrent primary headache disorder. Its attacks typically bring moderate to severe pain that is often one-sided and throbbing, and they are commonly accompanied by nausea and heightened sensitivity to light and sound. It is classified as a nervous system disorder, and its biology involves the brain, the blood vessels that supply it, and the sensory nerves that serve those vessels. Migraine is one of the most common and most disabling conditions in neurology, but its mechanisms are not fully resolved.
Clinical features
When untreated, an attack commonly lasts between 4 and 72 hours. Many attacks progress through several phases. The premonitory phase can begin hours or days before the headache and may include fatigue, mood changes, food cravings and sensitivity to light or sound. Some people then experience aura, a set of transient neurological symptoms, most often visual (such as zigzag lines or blind spots), sensory or speech disturbances, which usually develop gradually and resolve within about an hour. The headache phase follows, and the postdrome (resolution) phase can linger for a day or two, with tiredness and difficulty concentrating being common complaints.
Between attacks, many people have ongoing sensitivity to ordinary stimuli, which can make routine sensory input seem uncomfortable during the attack period.
Epidemiology
Migraine is one of the most prevalent disorders worldwide. Global age-standardised prevalence was estimated at 14.4% in 2016, with 18.9% in women and 9.8% in men, a female-to-male difference that is consistent across studies. The Global Burden of Disease 2021 estimates put the number of affected people above one billion. Migraine ranks among the leading causes of years lived with disability, and it is more disabling for women than for men.
Estimates of the trend are disputed. Some analyses report a rising number of cases over the past three decades, but a 2023 review argued that much of the apparent increase may reflect changes in diagnostic definitions and study methods rather than a true rise in prevalence. Prevalence also varies widely between countries and regions, and it is high among children and adolescents as well as adults.
Pathophysiology
Early explanations were vascular. In the mid-twentieth century, the vascular theory proposed that changes in cerebral blood vessels caused the headache, and it linked the aura to reduced blood flow. Later work emphasised the nervous system, and current models generally describe migraine as a neurovascular disorder in which neural and vascular processes interact.
Several components are thought to be involved:
- Brain excitability and sensory processing. Migraine is often described as a disorder of sensory processing in which the brain loses control over incoming signals. It is believed to arise from a cycling disturbance of brainstem and diencephalic systems, influenced by genetic predisposition and environmental triggers. Imaging studies have shown activity in the hypothalamus during the premonitory phase and during spontaneous headache.
- Cortical spreading depression. The aura is believed to reflect cortical spreading depression, a slow wave of neuronal depolarisation that moves across the cerebral cortex and is accompanied by changes in blood flow.
- The trigeminovascular system. Sensory neurons from the trigeminal nerve innervate the meningeal blood vessels, and their activation is central to the pain. Signals from these vessels involve the neuropeptide calcitonin gene-related peptide (CGRP), among others. Repeated activation can lead to sensitisation in both the peripheral and central nervous systems, which may help explain allodynia (pain from normally harmless touch) and the progression to chronic forms.
- Genetics and environment. Family and twin studies indicate a genetic component, although no single gene accounts for most cases. Hormonal fluctuations, sleep disruption, stress and dietary factors are among the triggers that have been studied.
Diagnosis
Migraine is diagnosed clinically, mainly from a detailed history of the attacks and their features, with the diagnostic criteria of the International Classification of Headache Disorders serving as the standard reference. No laboratory test or imaging finding is specific for migraine. Imaging is usually used to exclude other causes when symptoms are atypical, new in onset, or accompanied by warning signs.
Treatment
Treatment is divided into acute (attack) therapy and preventive therapy. Neither approach cures the disorder.
Acute treatment. Simple analgesics are commonly used first. Triptans, which are selective serotonin 5-HT1B/1D receptor agonists (serotonin receptor), were developed specifically for attacks. They are generally effective when taken early, but they are contraindicated in people with significant cardiovascular disease or uncontrolled hypertension because they can narrow coronary arteries. Gepants, which block the CGRP receptor, offer an alternative for acute treatment. Ditans, which act on the 5-HT1F receptor, are another option.
Preventive treatment. Many preventive drugs were originally developed for other conditions, such as high blood pressure, depression or epilepsy, and their effect on migraine was discovered later. CGRP-targeting drugs were the first agents developed specifically for migraine prevention. They include monoclonal antibodies against CGRP or its receptor, which are given by injection or infusion, and oral gepants. Botulinum toxin injections and neuromodulation devices, including non-invasive stimulation, are used in selected patients, and behavioural approaches such as cognitive behavioural therapy and biofeedback are often combined with medication.
Access to newer treatments is uneven. In some health systems, eligibility rules require that patients first fail several older preventive drugs before newer agents can be prescribed. Overuse of acute medication can produce medication-overuse headache, which complicates management.
Limitations and open questions
Several questions remain open. The full causal chain linking genetic susceptibility, brain activity and the pain of an attack is not established. The trend in prevalence is debated, and definitions have changed over time. Responses to treatment differ widely between individuals, and researchers continue to look for markers that could predict which drug will work for a given patient. Migraine in children and older adults, and the role of sex hormones across the life course, are also active areas of study.
References
- Migraine: from pathophysiology to treatmentncbi.nlm.nih.gov
- Pathophysiology of Migraine: A Disorder of Sensory Processingjournals.physiology.org
- Migraine: pathogenesis and pathophysiologymedlink.com
- Migraine Pathophysiology Revisited: Proposal of a New Molecular Theory of Migraine Pathophysiology and Headache Diagnostic Criteria - PMCpmc.ncbi.nlm.nih.gov
- Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain - PMCpmc.ncbi.nlm.nih.gov
- The Global Burden of Migraine: A 30-Year Trend Review and Future Projections by Age, Sex, Country, and Regionlink.springer.com
- Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 - The Lancet Neurologythelancet.com
- Global epidemiology of migraine and its implications for public health and health policynature.com
- Epidemiology of migraine - ScienceDirectsciencedirect.com
- CGRP therapy in primary care for migraine: prevention and acute medicationbjgp.org
- CGRP Inhibitors & Antagonist Drugs Listdrugs.com
- Methods for treating or preventing migraine headacheimage-ppubs.uspto.gov