Migraine’s primary symptom is sudden and intense headache usually on one side of the head. The brains of migraineurs are different in both their structure and function. Migraineurs who experience more migraines have more structural abnormalities including decreases in grey matter and lesions in white matter.

The functioning of the migraine brain is also atypical. Changes in the external and internal environments can trigger abnormal electrophysiological and vascular changes throughout the brain.

One neurophysiological explanation for migraines is cortical spreading depression. During cortical spreading depression, the electrical activity of neurons in a certain brain area is silenced. Once a certain threshold of depression occurs, this silencing spreads throughout the brain like a ripple in a pond.

Cortical spreading depression often begins in sensory associated brain areas such as those involved in vision. The origin in visual areas could explain the migraine aura, afflicting a third of migraineurs, which manifest as flickering lights or scintillating spots in the visual field preceding the onset of the headache.

Vasodilation, the dilation of blood vessels, in the brain appears to be another cause for migraines. The trigeminal nerve which is found at the bottom of brain is important for sensation in the face and motor functions such as biting and chewing. Upon the onset of headache in migraines, the trigeminal nerve will release a chemical called calcitonin gene-related peptide (CGRP). CGRP will relax the blood vessel walls causing vasodilation.

What are the treatments?

Finding effective treatments for migraine has been a challenge. Fifteen years ago, triptans represented an important step toward migraine attack resolution and symptomatic treatment. Triptans are drugs which bind to and activate specific serotonin receptors called 5-HT_1B and 5-HT_1D.

 Activating these receptors with triptans can have multiple effects. Triptans can impact trigeminal nerves involved in pain by decreasing the release of CGRP and substance P, a chemical known for its pain producing properties. Triptans can also modulate the activity of certain brain areas and induce vasoconstriction.

Five years ago botulin toxin, also known as BoTox®, was introduced as the first treatment for chronic migraine. BoTox® is usually thought of as a substance used for cosmetic surgery, but there is also evidence for its clinical potential. Botulin toxin may help headaches through multiple mechanisms. One mechanism describes how upon injection botulin toxin is taken up by cranial nerves in the face and travels up the trigeminal nerve into the central nervous system. Botulin toxin then reduces inflammation and inhibits the release of CGRP.

Five years ago botulin toxin, also known as BoTox®, was introduced as the first treatment for chronic migraine. BoTox® is usually thought of as a substance used for cosmetic surgery, but there is also evidence for its clinical potential.

The next milestone in migraine treatment arrived with the approval of CGRP monoclonal antibody therapy. Monoclonal antibody therapy involves the creation of antibodies that bind to a specific protein, in this case CGRP, or its receptor. When antibodies bind to these proteins or receptors it inactivates them. By inactivating CGRP, vasodilation caused by this molecule can be prevented.

Promising non-pharmacological therapeutic options are currently being assessed, but need to be validated. Noninvasive neurostimulation techniques, such as noninvasive vagal nerve stimulation, have shown potential in resolving migraine attack. Noninvasive vagal nerve stimulation involves the stimulation of the vagal nerve via a device that is placed on the skin of your neck.

Other non-pharmacological approaches, such as physical exercise or acupuncture, has demonstrated efficacy in small groups of patients and are worthy of further development through controlled trials.

There is a continual search for the various structural and functional abnormalities in the brain which generate such incredibly painful and debilitating events. Our knowledge on pathophysiology and therapeutic strategies is increasing over time, but the challenge of present and future studies is the improvement of migraine management to avoid the evolution toward a chronic form.

Interested in reading more? Be sure to check out the latest articles in BMC Neurology.