From the Guidelines
Migraines are caused by a complex interplay of genetic, neurological, and environmental factors, primarily involving abnormal brain activity affecting nerve signals, blood vessels, and chemicals like serotonin, as supported by the most recent expert consensus and literature review 1. The pathogenesis of migraine is widely believed to involve peripheral and central activation of the trigeminovascular system, and cortical spreading depression is thought to be the underlying neurophysiological substrate of migraine aura. Some key factors that contribute to the development of migraines include:
- Genetic predisposition, as migraine often runs in families
- Hormonal changes, especially in women
- Certain foods and drinks, such as aged cheese, alcohol, and caffeine
- Stress and sensory stimuli, like bright lights and strong smells
- Sleep disruptions and weather changes During a migraine, blood vessels in the brain dilate and release inflammatory substances, activating pain pathways and irritating the trigeminal nerve, which sends pain signals throughout the head. Understanding personal triggers and maintaining consistent routines with adequate sleep, regular meals, exercise, and stress management can help reduce migraine frequency and severity, as emphasized in the recent consensus statement on the diagnosis and management of migraine 1.
From the FDA Drug Label
Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system The cause of migraines is likely due to local cranial vasodilatation and/or the release of sensory neuropeptides through nerve endings in the trigeminal system 2.
- Key factors involved in migraines include:
- Cranial vasodilatation
- Release of sensory neuropeptides such as:
- Vasoactive intestinal peptide
- Substance P
- Calcitonin gene-related peptide
- Trigeminal system nerve endings
From the Research
Causes of Migraines
The causes of migraines are complex and involve a combination of genetic and environmental factors.
- Genetic changes in ion channels and environmental changes can render an individual more sensitive to environmental factors, leading to a migraine attack 3.
- Genome-wide association studies have identified approximately 40 genetic loci associated with migraine, and the genetic load is higher in familial migraine cases than in nonfamilial cases 4.
- Migraine is a complex familial disorder, and the severity and susceptibility of individuals are likely governed by several genes that vary between families 3, 4.
Pathophysiology of Migraines
The pathophysiology of migraines involves:
- A primary event in the central nervous system (CNS), probably involving a combination of genetic changes in ion channels and environmental changes 3.
- Activation of the trigeminovascular system and release of calcitonin gene-related peptide (CGRP) from the trigeminovascular system 3.
- Cortical spreading depression, which is a wave of abnormal brain activity that can trigger a migraine attack 3, 5.
Role of Genetics in Migraines
Genetics play a significant role in migraines, with:
- Family and twin studies showing a genetic component in migraine 6.
- Genetic profiling of predisposition to migraine facilitating the development of more effective diagnostic and therapeutic applications 6.
- Identification of genomic regions that increase individual risk to migraine in neurological, vascular, and hormonal pathways 5.