Migraine

Serotonin

Migraines are complex neurological disorders that involve headaches, sensitivity to light and sound, nausea, and cognitive disturbances. Research suggests that serotonin (5-HT) plays a major role in migraine development.

How Serotonin Affects Migraines

Serotonin helps regulate pain, blood vessel function, and inflammation in the brain. Changes in serotonin levels can trigger migraines through these mechanisms:

Serotonin Drops Before a Migraine Attack

• Normally, serotonin helps narrow (constrict) blood vessels.

• Before a migraine, serotonin levels drop, causing blood vessels to widen (dilate), leading to pain and inflammation.

Serotonin Affects Pain Sensitivity

• Low serotonin makes the nervous system more sensitive to pain.

• This explains why people with migraines often experience more intense pain than others.

Serotonin Imbalance Triggers Inflammation

• Low serotonin increases inflammation in the brain, worsening migraine symptoms.

Serotonin Regulates Sleep and Mood

• Poor serotonin levels can lead to sleep disturbances, depression, and anxiety, which are all linked to higher migraine frequency.

Noradrenaline

Noradrenaline is both a hormone and a neurotransmitter involved in the fight-or-flight response. It’s produced in the brainstem (especially the locus coeruleus) and adrenal glands. It affects blood vessels, heart rate, sleep-wake cycles, and pain perception.

How Noradrenaline Relates to Migraines

Pain Modulation

• Noradrenaline modulates pain through descending pain-inhibitory pathways in the brainstem.

• Low noradrenaline activity may reduce the effectiveness of these inhibitory pathways, contributing to the heightened pain sensitivity seen in migraine attacks.

• Low initiative, even for things you enjoy

• Difficulty concentrating or staying on task

• A general sense of “why bother?”

Vascular Effects

• Migraines, particularly migraine with aura, are linked to changes in cerebral blood flow.

• Noradrenaline causes vasoconstriction (narrowing of blood vessels). Dysregulation in noradrenaline could lead to abnormal vascular responses, possibly triggering or worsening migraines.

Stress and Cortisol Link

• Stress is a common migraine trigger, and noradrenaline is a major stress-response chemical.

• Chronic stress elevates noradrenaline, which can sensitize neurons, increase inflammation, and contribute to central sensitization, a key feature of chronic migraine.

Sleep and Wakefulness

• Noradrenaline is essential for regulating REM sleep and alertness.

• Poor sleep or irregular sleep-wake cycles are known migraine triggers, possibly through noradrenaline imbalance.

Trigeminal Nerve Interaction

• The trigeminal nerve is heavily involved in migraine pain.

• Noradrenaline influences this system and may either dampen or amplify nociceptive (pain) signals depending on receptor subtype activation.

Migraines are more than just severe headaches—they’re complex, neurological events often driven by hormonal imbalances. If you’re experiencing chronic migraines, When these hormones fall out of balance, your brain becomes more sensitive to pain, light, sound, and stress—creating the perfect storm for migraines.

Adrenaline

Adrenaline is your body’s emergency responder. It helps you power through stress, but too much or too little can backfire—especially on your brain.

In Migraine:

• Adrenaline surges often trigger migraine onset—especially after emotional stress or skipped meals.

• As levels drop, blood vessels dilate, leading to throbbing pain and fatigue.

Common Patterns:

• Migraine after arguments or stress

• Throbbing pain in temples or behind eyes

• Cold hands, racing heart, restlessness before attack

GABA: Your Brain’s Off Switch

GABA is the calming neurotransmitter that helps your brain slow down, rest, and recover.

In Migraine:

• Low GABA makes your brain hyper-reactive to light, sound, and sensory input.

• It also disrupts sleep quality, making recovery from migraines much harder.

Common Patterns:

• Auras or visual disturbances before migraine

• Poor sleep before or after attacks

• Heightened anxiety or sensory overwhelm

Glutamate

Glutamate is the brain’s primary excitatory neurotransmitter—it fuels neuron activity and plays a key role in pain perception, sensory processing, and vasodilation (blood vessel widening).

Glutamate's Role in Migraine

Triggering Cortical Spreading Depression (CSD)

• CSD is a wave of overactive neurons followed by a shutdown that spreads across the brain cortex—this is a core mechanism behind aura in migraines.

• Excess glutamate triggers CSD by overstimulating neurons, making the brain hyperexcitable and vulnerable to migraine onset.

Sensory Overload & Pain Amplification

Sensory Overload & Pain Amplification

• The trigeminal nerve pathways (pain highway for the face/head)

• The cortex and thalamus (sensory relay stations)

This leads to:

• Hypersensitivity to light, sound, smell (photophobia, phonophobia)

• Throbbing pain and nausea

• Aura symptoms in visual or sensory systems

Glutamate and Chronic Migraine

In people with chronic or frequent migraines, studies show persistently elevated glutamate levels in cerebrospinal fluid and blood.

This constant glutamate excess leads to:

• Lowered migraine threshold

• More frequent attacks

• Increased likelihood of transitioning from episodic to chronic migraine