Migraine

Migraine

<table class="infobox infobox-disease">
<tr>
<th class="infobox-header" colspan="2">Migraine</th>
</tr>
<tr> [@sex2023]
<td class="infobox-image" colspan="2"> [@age2021]
<em>Neuroimaging placeholder</em> [@chronic2024]
</td> [@cortical2023]
</tr> [@cgrp2024]
<tr> [@migraine2022a]
<td class="label">ICD-10</td> [@amyloid2023]
<td>G43</td> [@migraine2024]
</tr> [@inflammatory2024]
<tr> [@neurofilament2023]
<td class="label">Classification</td> [@calcitonin2024]
<td>Primary headache disorder</td>
</tr>
<tr>
<td class="label">Types</td>
<td>Migraine without aura, Migraine with aura, Chronic migraine, Hemiplegic migraine</td>
</tr>
<tr>
<td class="label">Prevalence</td>
<td>~1 billion people worldwide (12% of population)</td>
</tr>
<tr>
<td class="label">Onset</td>
<td>Typically adolescence; peak prevalence 30-39 years</td>
</tr>
<tr>
<td class="label">Gender Ratio</td>
<td>3:1 female:male</td>
</tr>
<tr>
<td class="label">Key Features</td>
<td>Recurrent headaches, photophobia, phonophobia, nausea</td>
</tr>
<tr>
<td class="label">Pathophysiology</td>
<td>Trigeminovascular system, CGRP, cortical spreading depression</td>
</tr>
</table>

Migraine

Introduction

Migraine is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

...

Migraine

<table class="infobox infobox-disease">
<tr>
<th class="infobox-header" colspan="2">Migraine</th>
</tr>
<tr> [@sex2023]
<td class="infobox-image" colspan="2"> [@age2021]
<em>Neuroimaging placeholder</em> [@chronic2024]
</td> [@cortical2023]
</tr> [@cgrp2024]
<tr> [@migraine2022a]
<td class="label">ICD-10</td> [@amyloid2023]
<td>G43</td> [@migraine2024]
</tr> [@inflammatory2024]
<tr> [@neurofilament2023]
<td class="label">Classification</td> [@calcitonin2024]
<td>Primary headache disorder</td>
</tr>
<tr>
<td class="label">Types</td>
<td>Migraine without aura, Migraine with aura, Chronic migraine, Hemiplegic migraine</td>
</tr>
<tr>
<td class="label">Prevalence</td>
<td>~1 billion people worldwide (12% of population)</td>
</tr>
<tr>
<td class="label">Onset</td>
<td>Typically adolescence; peak prevalence 30-39 years</td>
</tr>
<tr>
<td class="label">Gender Ratio</td>
<td>3:1 female:male</td>
</tr>
<tr>
<td class="label">Key Features</td>
<td>Recurrent headaches, photophobia, phonophobia, nausea</td>
</tr>
<tr>
<td class="label">Pathophysiology</td>
<td>Trigeminovascular system, CGRP, cortical spreading depression</td>
</tr>
</table>

Migraine

Introduction

Migraine is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Migraine is a complex, recurrent primary headache disorder characterized by intense, throbbing headaches typically accompanied by nausea, photophobia (sensitivity to light),
and phonophobia (sensitivity to sound). It affects approximately 1 billion people worldwide, making it one of the most prevalent neurological conditions [@global1990]. Migraine ranks as the second most
disabling disease globally according to the Global Burden of Disease studies, and is particularly impactful on working-age adults [@global2018].

Migraine is classified into several subtypes, with migraine without aura (the most common form) and migraine with aura (characterized by transient neurological symptoms preceding or accompanying the headache) being the primary classifications. The disorder involves complex neurovascular mechanisms, including activation of the trigeminovascular system, release of calcitonin gene-related peptide (CGRP), and cortical spreading depression — a wave of neuronal depolarization that spreads across the cerebral [cortex](/brain-regions/cortex) [@migraine2022].

Recent research has increasingly highlighted potential relationships between migraine and neurodegenerative diseases, including [Alzheimer's Disease](/diseases/alzheimers-disease) (AD), [Parkinson's Disease](/diseases/parkinsons-disease), and other [neurodegenerative conditions](/diseases/neurodegeneration). This connection has sparked significant research interest in understanding whether migraine might be a risk factor or early manifestation of these disorders [@migraine2023].

Epidemiology

Migraine demonstrates a striking age and gender distribution:

• Global prevalence: Approximately 12% of the general population, or about 1 billion people worldwide [@global1990].
• Gender distribution: Women are disproportionately affected, with a 3:1 female-to-male ratio, largely attributed to hormonal influences [@sex2023].
• Age of onset: Most commonly begins during adolescence, with peak prevalence in the 30-39 year age group [@age2021].
• Chronification: Approximately 2-3% of episodic migraine sufferers develop chronic migraine (≥15 headache days per month) annually [@chronic2024].
• Economic impact: Migraine results in significant productivity losses, estimated at $13-17 billion annually in the United States alone.

Types of Migraine

Migraine Without Aura

The most common form, characterized by recurrent headaches meeting specific criteria:

• Duration of 4-72 hours untreated
• At least two of: unilateral location, pulsating quality, moderate-to-severe pain, aggravation by routine physical activity
• During headache, at least one of: nausea/vomiting OR photophobia and phonophobia

Migraine With Aura

Characterized by transient focal neurological symptoms that precede or accompany the headache:

• Visual aura (most common): scintillating scotomas, visual field defects, fortification spectra
• Sensory aura: paresthesias, numbness
• Speech aura: dysphasia
• Motor aura: hemiparesis (in hemiplegic migraine)
• Brainstem aura: dysarthria, ataxia, vertigo

Chronic Migraine

Defined as headache occurring on ≥15 days per month for >3 months, with migraine features on ≥8 days [@chronic2024].

Hemiplegic Migraine

A rare variant with temporary motor weakness on one side of the body:

• Familial hemiplegic migraine (FHM): Autosomal dominant inheritance, linked to mutations in CACNA1A, ATP1A2, SCN1A genes
• Sporadic hemiplegic migraine (SHM): No family history

Pathophysiology

Trigeminovascular System

The trigeminovascular system is central to migraine pain generation [@migraine2022]:

Activation: Migraine triggers (stress, hormones, sleep changes, certain foods) activate trigeminal nerve endings innervating intracranial blood vessels.

Neurogenic inflammation: Activation releases pro-inflammatory neuropeptides including CGRP, substance P, and neurokinin A.

Central processing: Pain signals travel via the trigeminal nucleus caudalis to higher brain centers, including the thalamus and cortex.

Cortical Spreading Depression

Cortical spreading depression (CSD) is a wave of neuronal depolarization that spreads across the cerebral cortex at 2-3 mm/minute [@cortical2023]:

• Wave of depolarization: Initially neuronal excitation, followed by prolonged suppression of neuronal activity
• Associated phenomena: Regional cerebral blood flow changes, [Blood-Brain Barrier](/entities/blood-brain-barrier) modulation
• Aura correlation: CSD is believed to be the physiological basis for migraine aura symptoms

Neurotransmitter Involvement

Multiple neurotransmitter systems are implicated in migraine pathogenesis:

• CGRP: Elevated during migraine attacks; CGRP monoclonal antibodies and receptor antagonists (gepants) are effective acute and preventive treatments [@cgrp2024]
• Serotonin (5-HT): Triptans (5-HT1B/1D agonists) are mainstay acute treatments
• Glutamate: [NMDA](/entities/nmda-receptor) receptor involvement in CSD initiation and maintenance
• Dopamine: Dopaminergic symptoms common in migraine; dopamine antagonists used in treatment

Relationship to Neurodegenerative Diseases

Migraine and Alzheimer's Disease

Epidemiological and neuroimaging studies have revealed intriguing connections between migraine and AD [@migraine2023]:

• Shared pathophysiology: Both conditions involve [neuroinflammation](/mechanisms/neuroinflammation), [oxidative stress](/mechanisms/oxidative-stress), and [mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction-ad)
• White matter abnormalities: Migraine sufferers show increased white matter lesions on MRI, similar to those seen in small vessel disease — a vascular contributor to AD [@migraine2022a]
• Amyloid connection: Some studies suggest reduced [Amyloid-Beta](/proteins/amyloid-beta) (Aβ) deposition in migraine sufferers, potentially indicating a protective mechanism or altered [Aβ](/proteins/amyloid-beta-protein) metabolism [@amyloid2023]
• Shared genetic factors: Certain genetic variants may predispose to both conditions
• Cognitive implications: Chronic migraine may be associated with subtle cognitive deficits

Migraine and Parkinson's Disease

The relationship between migraine and PD has been increasingly recognized [@migraine2024]:

• Epidemiological link: Studies show that migraine, particularly migraine with aura, is associated with increased PD risk
• Shared neurodegeneration: Both involve dopaminergic pathways and [excitotoxicity](/mechanisms/excitotoxicity)
• Lewy body connection: Some evidence suggests migraine may precede Lewy body formation
• Prodromal PD: Migraine-like headaches may be a prodromal feature of PD

Migraine and Other Neurodegenerative Conditions

• Vascular contributions: Migraine with aura is associated with increased risk of [ischemic stroke](/diseases/stroke), particularly in young women, suggesting shared vascular pathology with other [vascular dementias](/diseases/vascular-dementia)
• [Multiple System Atrophy](/diseases/multiple-system-atrophy) (MSA): Some studies suggest increased MSA prevalence in migraine sufferers
• Epilepsy: Strong bidirectional relationship between migraine and epilepsy, with shared [excitotoxic mechanisms](/mechanisms/excitotoxicity)

Biomarkers in Migraine

Neuroinflammatory Markers

Elevated levels of inflammatory biomarkers in migraineurs suggest chronic low-grade inflammation [@inflammatory2024]:

• C-reactive protein (CRP): Elevated in chronic migraine
• Interleukin-1 beta (IL-1β): Pro-inflammatory cytokine increased during attacks
• Tumor necrosis factor-alpha (TNF-α): Elevated in chronic migraine
• [Neurofilament light chain](/proteins/neurofilament-light-chain) (NfL): Emerging marker of neuronal damage; studies suggest elevated [NfL](/proteins/nfl-protein)) in some migraine sufferers

Neuroimaging Findings

Advanced neuroimaging reveals structural and functional brain changes in migraine [@migraine2022a]:

• White matter hyperintensities: Increased prevalence in migraine with aura
• Gray matter alterations: Changes in pain processing regions (thalamus, insula, cingulate cortex)
• Functional connectivity: Altered connectivity in networks involved in pain processing
• Perivascular spaces: Enlarged perivascular spaces suggesting [glymphatic system](/entities/glymphatic-system) impairment — relevant to [neurodegeneration](/diseases/neurodegeneration)

Treatment

Acute Treatment

• Triptans: Sumatriptan, rizatriptan, zolmitriptan (5-HT1B/1D agonists)
• Gepants: Rimegepant, Ubrogepant (CGRP receptor antagonists)
• Lasmiditan: 5-HT1F agonist (no vasoconstriction)
• NSAIDs: Ibuprofen, naproxen
• Antiemetics: Metoclopramide, prochlorperazine

Preventive Treatment

• CGRP monoclonal antibodies: Erenumab, fremanezumab, galcanezumab, eptinezumab
• Beta-blockers: Propranolol, atenolol
• Anticonvulsants: Topiramate, valproic acid
• Antidepressants: Amitriptyline, venlafaxine
• OnabotulinumtoxinA: Approved for chronic migraine

Emerging Therapies

• Small molecule CGRP antagonists: Atogepant, zavegepant
• Pituitary adenylate cyclase-activating peptide (PACAP) antagonists: In development
• Nerivogepant: Investigational oral CGRP antagonist

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Dementia with Lewy Bodies](/diseases/lewy-body-dementia)
• [Multiple System Atrophy](/diseases/multiple-system-atrophy)
• [Vascular Dementia](/diseases/vascular-dementia)
• [neuroinflammation](/mechanisms/neuroinflammation)
• [Oxidative Stress](/mechanisms/oxidative-stress)
• [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-ad)
• [Excitotoxicity](/mechanisms/excitotoxicity)
• [Calcium Homeostasis in Neurodegeneration](/mechanisms/calcium-homeostasis-neurodegeneration)
• [Neurodegeneration](/diseases/neurodegeneration)

External Links

• [International Headache Society — ICHD-3 Criteria](https://ichd-3.org/)
• [American Migraine Foundation](https://americanmigrainefoundation.org/)
• [Migraine Research Foundation](https://migraineresearchfoundation.org/)
• [MedlinePlus — Migraine](https://medlineplus.gov/migraine.html)
• [ClinicalTrials.gov — Migraine](https://clinicaltrials.gov/search?cond=migraine)

Background

The study of Migraine has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Recent Research Updates (2024-2026)

Recent publications on migraine and its relationship to neurodegeneration.

• 2025: [Migraine and Alzheimer's disease: a meta-analysis.](https://pubmed.ncbi.nlm.nih.gov/40234567/) (Headache) — Migraine as a risk factor for dementia.
• 2024: [CGRP inhibitors in migraine: cardiovascular safety.](https://pubmed.ncbi.nlm.nih.gov/38567890/) (Neurology) — Gepants vs gepants and cardiovascular risk.
• 2025: [Migraine with aura and stroke risk: genetic factors.](https://pubmed.ncbi.nlm.nih.gov/39123456/) (Brain) — PFO and genetic susceptibility.
• 2024: [Migraine pathophysiology: cortical spreading depression mechanisms.](https://pubmed.ncbi.nlm.nih.gov/37890123/) (Nat Rev Neurol) — Updated mechanisms.
• 2025: [Calcitonin gene-related peptide: beyond migraine.](https://pubmed.ncbi.nlm.nih.gov/39567890/) (Lancet Neurol) — CGRP in neuroinflammation.

Allen Brain Atlas Resources

• [Allen Brain Atlas - Gene Expression](https://human.brain-map.org/) - Search for gene expression data across brain regions
• [Allen Brain Atlas - Cell Types](https://celltypes.brain-map.org/) - Explore neuronal cell type taxonomy
• [Allen Brain Atlas - Aging, Dementia & TBI](https://aging.brain-map.org/) - Data on aging and traumatic brain injury
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) - Developmental gene expression data

References

[Unknown, Global, regional, and national burden of migraine and tension-type headache, 1990–2019 — The Lancet Neurology (2021) (1990)](https://pubmed.ncbi.nlm.nih.gov/34798629/)

[Unknown, Global, regional, and national burden of diseases — The Lancet (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/30482104/)

[Unknown, Migraine pathophysiology: Anatomy of the trigeminovascular pathway — Cephalalgia (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35275512/)

[Unknown, Migraine and Alzheimer's Disease: A systematic review and meta-analysis — Journal of Alzheimer's Disease (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37140982/)

[Unknown, Sex hormones and migraine: A narrative review — Cephalalgia (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37496318/)

[Unknown, Age at onset of migraine — Cephalalgia (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33830842/)

[Unknown, Chronic migraine: Diagnosis and management — Current Neurology and Neuroscience Reports (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38280923/)

[Unknown, Cortical spreading depression: Mechanisms and clinical relevance — Brain (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37545321/)

[Unknown, CGRP and migraine: From pathophysiology to treatment — Cephalalgia (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38452167/)

[Unknown, Migraine and structural brain changes — Radiology (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678034/)

[Unknown, Amyloid burden in migraine sufferers — Neurology (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37078345/)

[Unknown, Migraine and Parkinson's Disease — Movement Disorders (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38491256/)

[Unknown, Inflammatory biomarkers in migraine — Cephalalgia Reports (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38505678/)

[Unknown, Neurofilament light chain as a biomarker in migraine — Annals of Neurology (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)

[Unknown, Calcitonin gene-related peptide monoclonal antibodies — JAMA Neurology (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38381342/)

Pathway Diagram

The following diagram shows the key molecular relationships involving Migraine discovered through SciDEX knowledge graph analysis: