Updated February 27, 2015.
Written or reviewed by a board-certified physician. See About.com's Medical Review Board.
Do you find yourself commiserating about headaches at family gatherings? Hopefully not! But, if so, this may be because headaches often run in families. If you suffer from incapacitating headaches, there is a good chance that your sister, cousin or mother does as well.
What is the Cause of Headaches?
Throughout the years, scientists have worked hard to uncover the etiology behind primary headache disorders like migraines, tension-type headaches, and cluster headaches.
The truth, though, is that primary headaches are complex medical disorders that do not have one single cause.
The majority of headaches are the result of multiple genetic and environmental factors interacting in a complicated web. While many of you work incessantly on controlling environmental factors through trigger avoidance and behavior modification, you obviously cannot change the genes you were born with. However, by studying the genetics involved in headache origination, scientists can create new drugs that target specific genes, in the hopes of curing, if not alleviating our burdensome and debilitating headaches.
What Types of Genes are Involved in Primary Headaches?
There is a significant role of inheritance in the development of primary headaches. This has been shown through multiple family and twin studies. But what are the actual genes being passed down? Most studies that have examined the genes involved in primary headaches have looked at genes that affect our vascular, nervous, and hormone systems.
Below is an example of two genes thought to play a role in the formation of primary headaches.
One gene is called the MTHFR gene, which stands for the long term, methylenetetrahydrofolate reductase. This gene is located on chromosome one and is involved in the homocysteine pathway. Homocysteine is an amino acid in our bloodstream that when elevated, may lead to blood vessel inflammation, as well as firing of certain nerve cells that may be involved in headaches. Certain mutations in this gene have been associated with both migraines and cluster headaches.
One study in Pharmacogenetics and Genomics found that in women with migraine with aura, vitamin supplementation significantly lowered their homocysteine levels, migraine severity, and migraine disability levels, compared to women who took placebo. Vitamin supplementation was done with vitamin B6, B9 (folic acid), and B12, which have been found to lower homocysteine levels in the bloodstream.
In addition, when the vitamin-treated group was examined closely, it was found that patients with a certain allele of the MTHFR gene had a significantly greater reduction in homocysteine levels, as well as migraine severity and disability scores, than those with a different allele. An allele is an alternative form of a gene that occupies a specific spot on a specific chromosome. This finding indicates that certain gene variants may influence how well migraineurs respond to vitamin supplementation.
TRPV1 (Transient Related Potential Vanilloid Type 1), as well several other members of the TRP (transient receptor potential) gene family, are expressed by trigeminal nociceptors, which are pain receptors in the facial area that have been linked to primary headaches, especially migraines. TRPV1, specifically, has been proposed to play a vital role in migraine sensitization, a term that refers to an overly sensitive or reactive nervous system in patients with migraines or other primary headaches.
This gene has also been studied to play a role in migraine hyperalgesia and allodynia, two conditions that can occur during a migraine attack. Hyperalgesia refers to an increased response to a painful stimulus and allodynia refers to a painful response to a normally harmless stimulus, such as feeling discomfort with a simple touch during a migraine attack. Over the past few years, drugs targeting the TRP channels have been studied as potential migraine therapies. One example of a drug that targets the TRPV1 channel that is commomly used to treat migraines is sumatriptan.
What is a Big Picture?
There are other genes linked to headache disorders, but the big picture here is that primary headaches, especially migraines, have a strong genetic basis. By learning more about the specific genes that predispose one to headaches, scientists can then target drugs to these genes.
Finally, understanding the genetic basis of many headache disorders may relieve some of the burden individuals experience, as they try to control their headaches. Consider discussing your family history with your healthcare provider, as this may provide some insight into your headaches and influence future therapy.
Sources
Evans MS, Cheng X, Jeffry JA, Disney KE, Premkumar LS. Sumatriptan inhibits TRPV1 channels in trigeminal neurons. Headache. 2012 May;52(5):773-84.
Meents JE, Neeb L, Reuter U. TRPV1 in migraine pathophysiology. Trends Mol Med. 2010;14(4):153–159.
Menon S, Lea RA, Roy B, Hanna M, Wee S, Haupt LM, Oliver C, Griffiths LR. Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation. Pharmacogenet Genomics. 2012 Oct;22(10):741-9.
Rainero, I. Rubino E, Paemeleire K, Gai A, Vacca A et al. Genes and primary headaches: discovering new potential therapeutic targets. J Headache Pain. 2013; Jul 12;14(1):61. 14(1): 61.
Russell MB. Genetics in primary headaches. J Headache Pain. 2007 Jun;8(3):190-5.
Svensson DA, Larsson B, Waldenlind E, Pedersen NL. Shared rearing environment in migraine: results from twins reared apart and twins reared together. Headache. 2003 Mar;43(3):235-44.
DISCLAIMER: The information in this site is for informational purposes only. It should not be used as a substitute for personal care by a licensed physician. Please see your doctor for advice, diagnosis, and treatment of any concerning symptoms or medical condition.
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