A Migraine’s Path Through The Nervous System

Many people are familiar with the physical symptoms of migraines, such as pain and sensitivity to light and sound. However, it is also important to understand what happens inside the brain during an attack. Scientists originally suspected that blood vessels on the brain’s surface dilated and constricted, causing the pulses of pain many sufferers feel. However, research has progressed to now implicate a deeper and more complex nerve pathway that then causes the vascular symptoms, and ultimately migraines. In this article, we will take a closer look at the entire path of a migraine from trigger to completion.

The Trigger

A migraine starts when the nerve cells in the brain are activated or triggered. A trigger can stem from a variety of causes, including dehydration, hunger, or lack of sleep. Nerves can also be activated by changes in nutrient levels, mitochondrial changes, or existing genetic abnormalities. Some headaches may not even have a clear trigger.  Regardless of how the nerve cell is activated, the brain will then move through a series of changes that lead to the all-too-familiar physical symptoms.

Neurons Activate

The location where headaches start in the body is not clear – it’s still an active area of research. What we do know is that neurons ultimately send messages along the trigeminal nerve pathway. This pathway connects nerves from the brainstem to nerves in the face, sinuses, and even inside the skull on the large blood vessels and the meninges (a layer of tough tissue surrounding the brain). The pain signals (also called neuropeptides) released from the triggered neurons cause blood vessels to dilate, which may explain the throbbing, pulsing pain many sufferers experience during an attack.

Neuropeptide Release

At a microscopic level, the brain responds to nerve triggers by releasing pain signals called neuropeptides.  Neuropeptides released in migraine include the calcitonin gene related peptide, pituitary adenylate cyclase activating peptide, and others. These signals travel to the meninges and lead to the inflammation.

Taking medications that block these neuropeptides may help migraines. There are eight medications that have come out in the last five years that block the calcitonin gene related peptide, and clinical trials are currently studying if migraines can be treated by blocking the pituitary adenylate cyclase activating peptide.  Many older medications for migraine, such as anti-seizure medications, anti-depressants, and blood pressure medications, alter the signaling of other chemicals in these headache pathways.

Central Nervous System Reacts

After the initial neuron activation (about 1-2 hours), the migraine will move into the next stage and the pain will change. In stage two, the central nervous system becomes involved and turns hypersensitive, causing additional symptoms and heightened pain.

Some migraine sufferers have been able to stop a migraine from progressing by taking medication before the second stage. If the pain cycle has progressed to the central nervous system, some medications may be less effective at relieving symptoms. This is why, for some patients, medications work very well if taken early in the headache, but not very well if taken later in the headache.

An untreated migraine can last up to 72 hours before the nervous system stops the response, and the brain recovers.  While the brain is recovering some patients still have symptoms, such as fatigue, that improve over time as the brain returns to normal.

Cortical Depression Spreads

We have discussed migraine pain, but we have not discussed the cause of auras, which are the visual, tactile, verbal, and other symptoms that many patients get before or during their headache. Auras are thought to be caused by a wave of electrical activity called cortical depression. This wave of electricity in the neurons slowly spreads across the surface of the brain from back to front. These contractions limit the flow of oxygen and may then cause pain.


Research is still ongoing to fully understand migraines and provide effective treatments to those who suffer from attacks. Scientists now have a greater understanding of what is physically occurring in the brain during a migraine attack, which moves them closer to finding a cure.

The Will Erwin Headache Research Foundation’s dedicated staff collaborates with leading healthcare specialists and researchers at The Will Erwin Headache Research Center in our relentless pursuit to find a cure for debilitating headaches, including migraines. If you would like to learn more about The Foundation and support the furtherance of headache research, consider contributing.