Evolving Understanding of Migraine Could Lead to New Treatments
Neurologists are learning more about the changes in bodily function – known as pathophysiology – that occur in people with migraines, which they say is key to identifying more effective treatments.
A migraine headache is usually characterized by intense, throbbing pain in one area of the head and may be accompanied by other symptoms, such as nausea, vomiting, or sensitivity to light and sound.
For many years, migraine was thought to be a blood vessel disorder because of the throbbing nature of the pain. However, recent studies have not supported the theory of a vascular cause.
Neurologists now believe migraines are caused by the sensory nerves on the outside of the brain.
“We found that people who have migraine, they have higher levels of pain neurotransmitters in their spinal fluid and in their nerves during a migraine and also between migraine attacks,” said Dr. Kerry Knievel, a neurologist and headache specialist at Barrow Neurological Institute.
Warning signs that precede migraines in some people, such as flashes of light, are thought to be caused by overstimulation followed by depression of nerves in the brain. Headaches are believed to result from inflammation activating pain pathways in the nervous system.
When the peripheral branches of the trigeminal nerve, which carries sensation from the face and scalp to the brain, and their associated blood vessels become inflamed, the trigeminal nerve releases neurotransmitters. These neurotransmitters, such as calcitonin gene-related peptide (CGRP), carry pain information from one neuron to another.
When the first-order neurons in the trigeminovascular system become activated, a process known as peripheral sensitization, the throbbing pain begins.
“This is where the reaction is much easier to stop,” said Dr. Chaouki Khoury, a neurologist at the Baylor Headache Center who recently spoke about migraine pathophysiology at Barrow. “If you treat early, you’re more likely to respond and abort your headache, and that’s because of our understanding of central sensitization and peripheral sensitization.”
Central sensitization occurs when neurotransmitters relay the pain information to the second-order neurons in the trigeminal nucleus, which resides in the upper portion of the brainstem. When these neurons become hyperexcitable, allodynia can occur. Allodynia is the triggering of a pain response to stimuli that do not normally provoke pain, such as a light touch.
Triptans, the first drugs developed specifically to target migraines, decrease the release of a specific neurotransmitter called serotonin and decrease the activation of neurons. However, triptans can only be used to abort a migraine headache that has already started.
We don’t know exactly how they work for prevention of migraine. The medications were being used for management of other problems in people who also happened to have migraine. Patients noticed that their headaches got better also, and the drugs were then studied for migraine prevention and proven to be effective.
-Dr. Kerry Knievel
People with frequent migraines may be given preventative treatments that were developed for other reasons but found to be effective in preventing migraine headaches. These treatments include blood pressure medications, anti-seizure medications, anti-depressants, and Botox injections.
“We don’t know exactly how they work for prevention of migraine,” Knievel said. “The medications were being used for management of other problems in people who also happened to have migraine. Patients noticed that their headaches got better also, and the drugs were then studied for migraine prevention and proven to be effective.”
But a current focus in migraine research is to develop a drug specifically to prevent and abort migraine headaches by targeting the neurotransmitter CGRP.
“There are some medications that actually prevent the release of the neurotransmitter and some that block the neurotransmitter from binding to its receptor, and those studies are in their final phases,” Knievel said.
More research is needed to understand what sets off the trigeminovascular system, but Khoury said genetics play a role.
“Understanding the pathophysiology better is really what’s going to lead to the development of treatments in the future, both to prevent and take away migraine,” Knievel said.