GENETICS & NEUROCHEMISTRY OF MIGRAINE

Migraine isn’t just about triggers or stress. For many people, it’s rooted in something much deeper — our genes and brain chemistry. This page explores how inherited traits, brain activity, and even hormones help shape the migraine experience.

GENETIC INSIGHTS

HEREDITARY PATTERNS & CHANNELOPATHIES

Familial hemiplegic migraine is linked to mutations in the CACNA1A gene on chromosome 19p13.
These mutations affect P/Q-type sodium channels, classifying this type as a channelopathy.
Migraine with aura may also have associations on chromosome 4Q.
Roughly 75% of people with this genetic variant have a family history of migraine.

PHYSIOLOGICAL PATHWAYS

BRAINSTEM ACTIVITY & VASCULAR CHANGES

Migraine is a neuronal event with vascular consequences.
The attack progresses through four phases: pre-headache (vasoconstriction), headache (vasodilation), late headache, and postdrome.
The trigeminovascular system plays a key role in transmitting pain.
Neurotransmitters like serotonin (5-HT) and substance P are involved in the pain cascade.
PET scans show brainstem activation during migraine attacks.

ENVIRONMENTAL & HORMONAL INFLUENCES

HORMONES, STRESS & DIETARY TRIGGERS

Estrogen and progesterone fluctuations influence migraine risk - especially in menstruation or pregnancy.
Certain people are unusually sensitive to tyramine, chocolate, alcohol, and red wine.
Emotional trauma or stress may trigger or intensify symptoms.
CGRP (calcitonin gene-related peptide) is a major player in migraine-related inflammation and blood vessel dilation.

MIGRAINE AURA THEORY

THE SPREADING DEPRESSION MODEL

Auras may be linked to Leão’s cortical spreading depression - a slow wave of nerve cell inhibition across the brain.
This causes temporary reduced blood flow, visual changes, and scintillating scotomas.
After the aura, hyperemia (increased blood flow) may follow.
Botulinum toxin (Botox®) may reduce migraine by affecting this peripheral nerve activation loop.

MIGRAINE AS A NEUROVASCULAR CONDITION

Migraine isn’t just about pain. It’s a complex brain-body interaction influenced by genetics, neurotransmitters, hormones, and even food. Understanding these pathways can help patients and healthcare providers choose more targeted, effective treatments.