pain

headaches & migraines

MEF2D

A Neurological Connection Between Stress and Migraines? (MEF2D)

Written by Jasmine Foster, BSc, BEd on August 13th, 2020

MEF2D may increase the activity of neurons and the incidence of migraines. Could your brain be more sensitive to pain signals? Find out here.

What is MEF2D?

The MEF2D gene encodes a protein called myocyte-specific enhancer factor 2D (also abbreviated MEF2D) [R].

MEF2D is a member of the Mef2 family of proteins. They are most active during the development of the embryo, but in adults, they help manage the stress response in nerve cells and, possibly, blood vessels [R, R].

MEF2D is currently being researched for its potential role in a number of diseases ranging from migraines to cancer [R].

What are Migraines?

Migraines are a type of headache that cause intense pain, usually accompanied by other symptoms like fatigue, stiffness, nausea, and sensitivity to light [R].

Migraine attacks can last for multiple days and typically go through three phases: the prodromal phase (before the headache), the headache phase, and the postdromal phase (after the headache) [R].

The prodromal phase may include extreme fatigue, nausea, muscle stiffness, extreme sensitivity to light, and other symptoms. Some people may also experience a visual phenomenon called aura, in which the sufferer may have blind spots, or see flashes of light or colour [R].

Could MEF2D Promote Migraines?

MEF2D promotes cell growth and division and is believed to directly influence brain activity. More specifically, some research suggests that MEF2D increases neuronal excitability, or the rate at which neurons fire in the brain, by increasing their sensitivity to stimuli [R].

Some studies suggest that migraines may be caused by imbalances in the relative sensitivity of neurons; highly active neurons may be at the root of painful migraine attacks [R, R, R].

MEF2D is a protein that may increase the activity of neurons, which may in turn increase the incidence of migraines.

MEF2D Variants & Migraine

Several variants in MEF2D have been associated with migraine. Of these, some have been found to have a small but significant link to migraine (rs2274316-C, rs1925950-G, rs12136718-A), while others appear to have more dramatic effects [R, R, R].

Two variants with potentially larger effects are rs3790455 and rs1050316. The minor ‘C’ allele at rs3790455 and the minor ‘G’ allele at rs1050316 have each been linked to significantly higher rates of migraine [R, R].

Your MEF2D Results for Migraine

SNP Table

variant	genotype	frequency	risk allele
rs2274316
rs12136718
rs1925950
rs3790455
rs1050316

SNP Summary and Table

MEF2D rs2274316

‘A’ = Associated with slightly lower incidence of migraine
‘C’ = Associated with slightly higher incidence of migraine

MEF2D rs12136718

‘G’ = Not associated with increased incidence of migraine
‘A’ = Associated with slightly higher incidence of migraine

MEF2D rs1925950

‘A’ = Associated with slightly lower incidence of migraine
‘G’ = Associated with slightly higher incidence of migraine

MEF2D rs3790455

‘T’ = Associated with lower incidence of migraine
‘C = Associated with higher incidence of migraine

MEF2D rs1050316

‘T’ = Associated with lower incidence of migraine
‘G’ = Associated with higher incidence of migraine

Recommendations

Lifestyle

Cold

Applied heat activates the TRPV1 heat pain receptor, which in turn increases MEF2D expression. One way to reduce TRPV1 activation is by activating its opposing cold receptor, TRPM8 [R, R].

Cold therapy has also been used in the treatment of migraines for over 150 years. Different devices applying cold to the head and neck have been successfully tested in several clinical trials [R, R, R, R, R, R].

Applied cold may soothe migraine pain by reducing the activation of the TRPV1 heat pain receptor, which in turn decreases MEF2D expression.

Stress Management

MEF2D is believed to play a role in stress management and may be activated in response to psychological stress. Stress has also been proposed as a migraine trigger, and stress management strategies may help reduce the incidence of migraines in people who are susceptible to them [R, R].

Stress and the perception of threats are also believed to increase pain. The following mental/emotional factors can affect pain [R, R, R]:

Thoughts
Emotions
Social and familial support
Cultural background
Context and memory associated with the pain

Clinical hypnosis can reduce pain in adults and children, and has been observed to reduce migraines [R, R].

MEF2D may be activated in response to psychological stress; stress management strategies are therefore recommended to help reduce pain.

Diet

Coffee and Tea

Caffeine is a part of different FDA-approved drugs for migraine and tension headaches, along with Tylenol, aspirin, sumatriptan, diclofenac, and others [R, R, R, R, R, R, R].

Oddly, caffeine has actually been found to increase MEF2D gene expression in muscle cell studies. However, these studies have no bearing on what caffeine may do to MEF2D in the brain. Future studies are needed to clarify this relationship [R, R].

In 2 clinical trials on almost 350 people, caffeine (both oral and intravenous) helped prevent postoperative headaches [R, R].

Ironically, headache is one of the most common symptoms of caffeine withdrawal, which can be a limitation for its long-term use [R].

The most significant dietary sources of caffeine are coffee and black tea.

Despite its effect on MEF2D in muscle cells, caffeine is included in many FDA-approved migraine medications. Caffeine may have a completely different effect in neurons than in muscle cells.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More pain blogs

Can This Gene Worsen GERD Pain? (GNB3) Can This Gene Make You Prone to Chronic Pain (COMT)? The Heat Receptor’s Role in Pain Perception (TRPV1) Can This Gene Influence Your Sensitivity To Pain (COMT)? A Neurological Connection Between Stress and Migraines? (MEF2D) Can This Gene Influence Your Susceptibility To Headaches And Migraines? (BDNF) Is Excess Histamine Causing Your Migraines? (DAO) Can Too Much Nitric Oxide Trigger Migraines? (NOS2, NOS3)

More headaches & migraines blogs

Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT) A Neurological Connection Between Stress and Migraines? (MEF2D) Is Excess Histamine Causing Your Migraines? (DAO) Can This Folate-Metabolizing Gene Increase Your Risk Of Headaches And Migraines? (MTHFR)

Content

What is MEF2D? MEF2D Variants & Migraine Your MEF2D Results for Migraine

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