Will Migraine Gene Discovery Provide Pain Relief?

Will Migraine Gene Disovery Provide Pain Relief?

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction.   In the words of a migraine sufferer, "it feels like the top of my head is going to explode, even the  softest whisper reverberates in my head and the tiniest bit of light feels like shards of glass in my eyeballs." 

While there are medications specifically to treat migraines, and some causes or triggers for onset of migraines have been identified, it is unclear why certain individuals are susceptible to migraines, while many others never experience a migraine in their entire life.

Scientists  believe they have identified the first-ever genetic risk factor for common migraines based on a specific variation in a section of DNA that helps to control a brain chemical called glutamate.  

In a statement, Dr Aarno Palotie, Chair of the International Headache Genetics Consortium, Wellcome Trust Sanger Institute said, "This is the first time we have been able to peer into the genomes of many thousands of people and find genetic clues to understand common migraine."

Having previously linked genetic mutations to rare and extreme forms of migraine, this is the first time researchers have identified one gene that leads to the more common forms of these debilatating headaches.

Reported in the current edition of the journal Nature Genetics researchers compared the genomes of more than 3,000 Europeans with a sample population of 10,000 people who don't experience migraines.   Patients with a variation on chromosome 8 between two genes called PGCP and MTDH/AEG-1 were significantly more likely to develop common migraines. 

Focusing on a gene known as EAAT2 and an associated protein responsible to remove glutamate from the connections in the brain, scientists believe a buildup of glutamate in the brain's nerve cell connections may be the root cause of migraines.  Glutamate is a neurotransmitter sending messages to and from the nerve cells in the brain.

While cautious about drawing conclusions, researchers believe that preventing glutamate buildup at the brain's nerve cell junctions may help prevent migraines.

The genetic risk factor "rs1835740" identifies common migraines with visual disturbances, and disrupts  activities in certain cells that control EAAT2, which has been identified in other neurological diseases such as epilepsy, schizophrenia and various mood and anxiety disorders.

"Although we knew that the EAAT2 gene has a crucial role to play in neurological processes in human and potentially in the development of migraine, until now, no genetic link has been identified to suggest that glutamate accumulation in the brain could play a role in common migraine."  Christian Kubisch, University of Ulm, Germany, said in a news release.  "This research opens the door for new studies to look in depth at the biology of the disease and how this alteration in particular may exert its effect."

The National Headache Foundation (NHF) website  says, "Many factors can trigger migraine attacks, such as alteration of sleep-wake cycle; missing or delaying a meal; medications that cause a swelling of the blood vessels; daily or near daily use of medications designed for relieving headache attacks; bright lights, sunlight, fluorescent lights, TV and movie viewing; certain foods; and excessive noise. Stress and/or underlying depression are important trigger factors that can be diagnosed and treated adequately."

Migraine characteristics can include:

    * Pain typically on one side of the head
    * Pain has a pulsating or throbbing quality
    * Moderate to intense pain affecting daily activities
    * Nausea or vomiting
    * Sensitivity to light or sound
    * Attacks last four to 72 hours, sometimes longer
    * Visual disturbances or aura
    * Exertion such as climbing stairs makes headache worse

Many factors can trigger migraine attacks, such as alteration of sleep-wake cycle; missing or delaying a meal; medications that cause a swelling of the blood vessels; daily or near daily use of medications designed for relieving headache attacks; bright lights, sunlight, fluorescent lights, TV and movie viewing; certain foods; and excessive noise. Stress and/or underlying depression are important trigger factors that can be diagnosed and treated adequately.

Migraine characteristics can include:

    * Pain typically on one side of the head
    * Pain has a pulsating or throbbing quality
    * Moderate to intense pain affecting daily activities
    * Nausea or vomiting
    * Sensitivity to light or sound
    * Attacks last four to 72 hours, sometimes longer
    * Visual disturbances or aura
    * Exertion such as climbing stairs makes headache worse

"Approximately one-fifth of migraine sufferers experience aura, the warning associated with migraine, prior to the headache pain. Visual disturbances such as wavy lines, dots or flashing lights and blind spots begin from twenty minutes to one hour before the actual onset of migraine. Some people will have tingling in their arm or face or difficulty speaking. Aura was once thought to be caused by constriction of small arteries supplying specific areas of the brain. Now we know that aura is due to transient changes in the activity of specific nerve cells."

The Food and Drug Administration (FDA) has approved three over-the-counter products to treat migraine, Excedrin® Migraine, Advil® Migraine and Motrin® Migraine Pain.  Also FDA approved are four prescription drugs for migraine prevention,  propranolol (Inderal®), timolol (Blocadren®), topiramate (Topamax®) and divalproex sodium (Depakote®). These have had many years of use and make up the majority of the items considered 'first line' therapy for migraine prevention.

NHF reports, "More than 29.5 million Americans suffer from migraine, with women being affected three times more often than men. This vascular headache is most commonly experienced between the ages of 15 and 55, and 70% to 80% of sufferers have a family history of migraine. Less than half of all migraine sufferers have received a diagnosis of migraine from their healthcare provider. Migraine is often misdiagnosed as sinus headache or tension-type headache."

The initial discovery of a genetic link to migraines, which could lead to more precise diagnosis and treatment, is monumental for those suffering from chronic debilitating migraine headaches.