Historically, it was believed that the pain of migraine headaches resulted from an expansion of the large blood vessels (vasodilation) supplying the brain. This expansion led to a stretching of the nerve fibers attached to these vessels, which led to the perception of pain. Migraine headaches treatments were aimed at constricting these blood vessels.
Experiments in the early 1990s showed that when these nerves are activated, they also release neurotransmitters that cause dilation and inflammation of blood vessels. This interaction between neurotransmitters and the blood vessels is felt to take place in the trigemino-vascular junction.
The nerve fibers that surround the blood vessels are branches of the trigeminal nerve. When they are activated, electrical impulses travel along the trigeminal nerve into the lower brain stem, which is the most primitive portion of the brain. The brain stem is only about the size of your thumb, but many functions take place in this area of the central nervous system.
The trigeminal nerve has three branches: the ophthalmic division, which supplies the area around the eye and the forehead; the maxillary division, which supplies the cheek and the upper jaw; and the mandibular division, which supplies the lower jaw. This information is then passed on to cells that also receive information from the head, face, scalp, sinuses and neck.
Once the cascade is started, migraine headache sufferers will experience migraine headaches symptoms such as neck pain, scalp tenderness, facial pain, eye swelling, tearing, and nasal dripping. Many scientists also believe that the neurons in the brain are hyper-excitable in between migraine attacks. This hyper-excitable state makes these cells more susceptible to the processes leading to a migraine headache.
The membranes surrounding these cells have microscopic channels through which electrolytes pass and to which neurotransmitters attach, leading to a series of chemical reactions. When these channels are abnormal, it is referred to as a channelopathy. Migraines may be a type of channelopathy.
These channelopathies make the neurons unstable and susceptible to spontaneous activation or dysfunction. If this dysfunction occurs on the surface of the brain, a slowly moving electrical “wave” may spread across the brain in what is referred to as spreading cortical depression. This is experienced as an aura migraine by many people.
A migraine with aura may be accompanied by flashing, jagged lights or migraine aura zig zag lines moving slowly across the field of vision. Cortical spreading depression is capable of activating trigeminal nerve fibers, a mechanism that explains why a migraine headache often occurs after the aura has started.
Many substances and receptors play roles in the propagation of a migraine. Calcitonin gene-related peptide (CGRP) is known to be released from trigeminal nerve endings during a migraine attack. This neurotransmitter is thought to be the main culprit in causing the dilation of blood vessels.
Among the most important receptors are the serotonin or 5-hydroxytryptamine (5-HT) receptors that sit on the blood vessels and tips of the trigeminal nerve endings. Newer drugs used to treat migraine, known as triptans, specifically attach to these 5-HT receptors, leading to the constriction of blood vessels.
With a better understanding of the causes of migraine headaches, migraine headaches are now recognized as a neurological disease. This has resulted in more attention and resources being aimed at developing and advancing the treatment for migraine headaches.
For a better understanding of the chemical changes in the brain that cause migraines, watch the video below: