Why Do I Keep Getting Migraines? Understanding What Happens in the Brain
Migraines are not “just a headache.” They are a complex neurological disorder involving a cascade of physiological, biochemical, and neurovascular events in the brain.
While the exact cause of a migraine attack remains incompletely understood, decades of research have clarified that migraines originate from dysregulation within the central nervous system and involve multiple interacting brain structures, neurotransmitters, and sensory circuits.
In this comprehensive article, we explore what science currently understands about the mechanisms underlying migraines — from genetic predisposition and brainstem dysfunction to cortical electrical activity and neuropeptide signaling.
What Is a Migraine?
A migraine is a recurrent episodic disorder characterized by moderate to severe head pain often accompanied by nausea, vomiting, sensitivity to light (photophobia), sound (phonophobia), and, in some people, transient visual or sensory disturbances known as aura.
It affects an estimated 10-15% of people worldwide and is one of the most common disabling neurological conditions in adults (NCBI Bookshelf - Migraine Headache).
Migraines are more than pain alone; they are dynamic neurobiological events that unfold in phases and involve widespread alterations in brain function across several structures and networks.
Genetic Factors and Brain Vulnerability
Migraine has a strong genetic component. Many people with migraine have family members who also experience the disorder, and genetic studies have identified numerous gene variants associated with an increased susceptibility to migraine attacks.
While these genes are diverse, many relate to neuronal excitability, ion channel function, and neurotransmitter regulation, which supports the view that migraine is fundamentally a neuroelectrical disorder of the brain (PubMed - Pathophysiology of Migraine).
Genetic predisposition does not act alone; environmental factors, lifestyle, hormones, and stress may interact with genetic risk to produce the conditions that allow a migraine attack to begin.
The Brainstem and Pain Modulation
Early research into migraines focused on blood vessels in the brain; however, modern neuroscience has shifted understanding toward neural mechanisms.
Studies using functional imaging have shown abnormal activation in specific brainstem regions during migraine attacks, including the periaqueductal gray (PAG) and locus coeruleus. These regions are involved in pain modulation and sensory integration, and dysfunction here may contribute to heightened sensitivity to pain and sensory stimuli in migraineurs (PMC - Pathophysiology of Migraine).
The brainstem also interacts with sensory pathways and the trigeminal pain system, establishing a lowered threshold for pain signals to reach conscious perception.
Neurovascular Interactions: More Than Blood Vessels
Although old theories proposed that migraines were caused by changes in blood vessel diameter, current evidence suggests that vascular changes are a downstream effect rather than the primary trigger (Johns Hopkins Medicine).
Today, researchers view migraines as a neurovascular disorder: neuronal dysfunction triggers neurochemical and vascular responses, but the pain and other symptoms originate in the nervous system, not in the blood vessels themselves.
One of the key neurovascular mechanisms is the activation of the trigeminovascular system, a nerve network that surrounds cranial blood vessels and transmits pain signals from the meninges (the protective membranes covering the brain). When this system is activated, nociceptive neurons release potent neuropeptides that sensitize pain pathways and induce inflammation and vasodilation.
Role of Calcitonin Gene-Related Peptide (CGRP)
One of the most important molecules in migraine pathophysiology is calcitonin gene-related peptide (CGRP).
When trigeminal nerves are stimulated, CGRP is released and acts as a powerful vasodilator and pronociceptive messenger, amplifying pain signals and promoting inflammation in pain pathways.
Drugs that block CGRP or its receptor have emerged as effective migraine preventive treatments, further underscoring the central role of this peptide in migraine biology (Mayo Clinic - Migraine Causes).
Cortical Spreading Depression (CSD)
Cortical spreading depression is a phenomenon involving a slowly propagated wave of neuronal and glial depolarization followed by long-lasting suppression of brain activity.
CSD is closely linked to the aura symptoms experienced by some individuals and may also play a role in triggering pain pathways by releasing inflammatory mediators and altering extracellular ion balances.
Although not every migraine involves aura, CSD provides a powerful model for understanding how widespread changes in neuronal activity can initiate a migraine episode (Integrated Health Foundation).
CSD begins in a focal point in the cortex and spreads across brain regions, disrupting normal electrical and biochemical homeostasis. This disturbance can activate the trigeminovascular system and lower the threshold for pain signal transmission from the meninges to higher brain centers.
Neurochemical Imbalances and Sensory Sensitization
Migraine attacks are accompanied by changes in the levels of key neurotransmitters and neuromodulators.
One of the most studied is serotonin (5-HT), a chemical that helps regulate pain and vascular tone.
Changes in serotonin levels are thought to play a role during attacks, and medications that increase serotonin activity (such as triptans) can abort the migraine by reducing neurogenic inflammation and stabilizing trigeminal signaling.
Other neurochemicals — including norepinephrine, dopamine, nitric oxide, and various peptides — also play roles in modulating pain sensitivity and vascular responses during migraines.
Central Sensitization and Hypersensitivity
One hallmark of migraine is the amplification of normal sensory inputs into painful or intolerable sensations — a process known as central sensitization.
During an attack, neurons in pain pathways become hyper-responsive, so stimuli that would not normally be painful (light, noise, gentle touch) are perceived as aversive or painful.
Central sensitization explains why migraine sufferers experience photophobia (light sensitivity), phonophobia (sound sensitivity), and allodynia (pain from normally non-painful touch).
It reflects an inability of brain networks to appropriately modulate incoming sensory information, leading to an overwhelming alarm response.
The Four Phases of a Migraine Attack
1. Premonitory Phase
This phase can begin hours or days before the headache.
Symptoms may include mood changes, food cravings, fatigue, neck stiffness, and increased sensory sensitivity.
It reflects early brainstem and hypothalamic activity changes that precede overt pain.
2. Aura Phase
Not all migraineurs experience aura, but in those who do, it typically features reversible visual or sensory phenomena that follow the spread of cortical depolarization across the brain's cortex.
Aura symptoms provide direct evidence of transient alterations in brain electrical function and neuronal excitability.
3. Headache Phase
This is the classic migraine pain stage, involving activation of trigeminal pain pathways, release of CGRP and other neuropeptides, and sensitization of central pain circuits.
During this phase, neural networks that regulate pain and sensory processing are highly dysregulated.
4. Postdromal Phase
After the main pain subsides, many people experience lingering fatigue, cognitive fog, or sensory sensitivity — reflecting ongoing recovery of neuronal networks toward baseline function.
Triggers: Provokers, Not Causes
Many people with migraines identify “triggers” such as certain foods, stress, bright lights, or sleep disturbances.
It's important to understand that while triggers may provoke an attack, they are not the fundamental cause of migraine.
Rather, they interact with an already vulnerable brain — one with altered sensory processing — to lower the threshold for an attack to begin.
Those triggers include hormonal changes (especially in women), weather changes, bright or flickering lights, strong smells, stress, certain foods and beverages, and sleep disruption — all conditions that perturb neural homeostasis and sensory regulation.
Why Women Are More Affected
Sex differences in migraine prevalence are striking: women are approximately three times more likely than men to suffer migraines.
Hormonal fluctuations, particularly estrogen variation across the menstrual cycle, pregnancy, or menopause, are thought to influence serotonin and neuronal excitability, contributing to increased migraine susceptibility.
Non-Pain Symptoms: Beyond Headache
Migraine affects multiple brain systems, which explains accompanying symptoms such as nausea, vomiting, light and sound sensitivity, and mood changes.
The involvement of brainstem nuclei, hypothalamic pathways, and limbic structures explains why migraines can impact appetite, emotional regulation, sleep, and autonomic function.
Treatment and Preventive Strategies
Treating migraines involves both abortive therapies — which stop an attack in progress — and preventive therapies designed to reduce attack frequency and severity.
Abortive treatments include triptans, NSAIDs, and antiemetics.
Preventive strategies include lifestyle modification, identifiable trigger management, and medications targeting serotonin pathways or CGRP signaling.
Recent advances include monoclonal antibodies that block CGRP or its receptor and small-molecule CGRP receptor antagonists, which have shown efficacy in preventing migraine attacks, reflecting how understanding physiological mechanisms informs new treatments.
When to Seek Medical Attention
Seek medical care if you experience sudden severe headaches, neurological deficits, new-onset headaches after age 50, or worsening frequency or intensity of migraines.
Conclusion
Migraines are complex neurological events that reflect dysregulated brain function rather than simply dilated blood vessels or “bad headaches.”
Genetic predisposition, brainstem and cortical mechanisms, neurochemical imbalances, sensory sensitization, and neurovascular signaling all contribute to the pathophysiological process.
While triggers may initiate an attack, the underlying cause lies in an altered brain state with heightened sensitivity to change.
Continued research into migraine physiology holds promise for improved diagnoses, personalized treatments, and better quality of life for sufferers worldwide.
Disclaimer: This article is for educational purposes only and is not a substitute for professional medical advice. Consult your healthcare provider for personalized guidance.
Frequently Asked Questions About Migraines
What causes migraines to happen?
Migraines are caused by complex interactions in the brain involving abnormal neuronal activity, changes in neurotransmitters, and activation of pain pathways.
They are considered a neurovascular disorder involving the trigeminovascular system rather than just a problem with blood vessels.
What happens in the brain during a migraine?
During a migraine, there is altered brain activity, including cortical spreading depression, activation of pain pathways, and release of neuropeptides like CGRP.
These processes lead to inflammation, heightened pain sensitivity, and the characteristic symptoms of migraine.
Why do some people get migraines more often than others?
Genetic factors play a significant role in migraine susceptibility, affecting how the brain processes sensory signals and regulates neurotransmitters.
Environmental triggers such as stress, sleep changes, and hormonal fluctuations can further increase the likelihood of attacks.
Are migraines just severe headaches?
No, migraines are more than headaches. They are a neurological condition that can include symptoms such as nausea, sensitivity to light and sound, and visual disturbances.
The pain is only one part of a broader set of brain-related changes occurring during an attack.
What triggers a migraine attack?
Common triggers include stress, lack of sleep, hormonal changes, certain foods, dehydration, and environmental stimuli like bright lights.
Triggers do not directly cause migraines but can lower the brain’s threshold for initiating an attack.
Can migraines be prevented?
While migraines may not always be completely preventable, their frequency and severity can often be reduced.
Preventive strategies include lifestyle modifications, avoiding known triggers, and using medications when prescribed by a healthcare provider.
References
- NCBI Bookshelf - Migraine Headache
- PubMed - Pathophysiology of Migraine (Nazia Karsan)
- PMC - Pathophysiology of Migraine
- Johns Hopkins Medicine - How a Migraine Happens
- Mayo Clinic - Migraine Causes
- Integrated Health Foundation - Migraine Mechanism
How we reviewed this article:
Our team continually updates articles whenever new information becomes available.
Written and Medically Reviewed by Ian Nathan, MBChB Candidate, on 16th March 2026
