267 | id == 267
267 | category_id == 19
267 | category_order == 16
267 | category_name == Pain
267 | category_color == #C47AC0
267 | slug == COMT-pain-sensitivity
267 | title == Can This Gene Influence Your Sensitivity To Pain (COMT)?
267 | meta_description == The COMT gene breaks down many important types of neurotransmitters, and is associated with pain sensitivity. Learn more here!
267 | summary == <p style="text-align:justify"><strong>The COMT gene encodes a protein that breaks down norepinephrine, epinephrine, and dopamine. Variants with low activity increase the levels of these neurotransmitters, and have been associated with increased sensitivity to pain. Read on to learn where your COMT gene stands!</strong><br />  &nbsp;</p>
267 | overall_score_text == Your Pain Sensitivity Score (based on COMT Gene)
267 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/COMT--Pain-Pain-Sensitivity.jpg
267 | author_id == 12
267 | author_name == Carlos Tello
267 | author_title == PhD
267 | author_order == 55
267 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
267 | author_intro == <p><strong>Carlos received his PhD and MS from the Universidad de Sevilla.</strong></p>    <p>Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.</p>
267 | author_social_media_name == linkedin
267 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
267 | author_social_order == 1
267 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
267 | reviewer_id == 14
267 | reviewer_name == Shany Lahan
267 | reviewer_title == MS (Neuroscience)
267 | medical_reviewer_id == 11
267 | medical_reviewer_name == Puya Yazdi
267 | medical_reviewer_title == MD
267 | publish_date == 2020
267 | publish_date == 8
267 | publish_date == 12
267 | avg_rating == 5.0
267 | tags_id == 65
267 | tags_name == COMT Gene
267 | tags_id == 51
267 | tags_name == Dopamine
267 | tags_id == 53
267 | tags_name == Epinephrine
267 | tags_id == 52
267 | tags_name == Norepinephrine
267 | tags_id == 598
267 | tags_name == Opioids
267 | tags_id == 71
267 | tags_name == Pain
267 | tags_id == 601
267 | tags_name == Pain Sensitivity
267 | tags_id == 603
267 | tags_name == Postoperative Pain
267 | tags_id == 602
267 | tags_name == Sickle Cell Disease
267 | permissions_favorite == False
267 | permissions_rate == False
267 | content_article == <p><em><span style="font-weight: 400;">If you have persistent or unexplained pain, it is important to discuss these concerns with your doctor. The information in this post is presented for educational purposes only, and should not be used to replace standard medical care.</span></em></p> <h2><strong>What Is the <em>COMT </em>Gene?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/comt/"><em><span style="font-weight: 400;">COMT</span></em></a> <span style="font-weight: 400;">gene codes for an enzyme called </span><em><span style="font-weight: 400;">catechol-o-methyltransferase</span></em><span style="font-weight: 400;"> (also called COMT). As its name implies, COMT transfers a methyl group to catechol-containing compounds. COMT uses </span><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">SAM-e</span></a><span style="font-weight: 400;"> as its methyl donor. Therefore, having either too little SAM-e, or too much S-adenosylhomocysteine (SAH) &mdash; which is formed when SAM-e loses its methyl group &mdash; results in inhibition of COMT [</span><a href="https://pubmed.ncbi.nlm.nih.gov/8576124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/12371153/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The main function of COMT is to help break down </span><em><span style="font-weight: 400;">catecholamines</span></em><span style="font-weight: 400;">, a family of neurotransmitters that includes </span><a href="https://selfhacked.com/blog/dopamine/"><span style="font-weight: 400;">dopamine</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">norepinephrine</span></a><span style="font-weight: 400;"> (also known as </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">noradrenaline</span></a><span style="font-weight: 400;">), and epinephrine (also known as adrenaline) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16878403/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">COMT is widely distributed throughout the body, including in regions associated with pain perception, such as the prefrontal cortex of the brain, the spinal cord, and peripheral nerves [</span><a href="https://pubmed.ncbi.nlm.nih.gov/9760135/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/8783248/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The <em>COMT </em>gene encodes an enzyme of the nervous system that breaks down the neurotransmitters dopamine, norepinephrine, and adrenaline by transferring a methyl group to them, from SAM-e.</span></p> <h3><strong>COMT Function and Pain Perception</strong></h3> <p><span style="font-weight: 400;">Studies in gene-edited mice have reported that mice which overproduced COMT enzymes had increased pain tolerance, whereas mice lacking this protein were more sensitive to acute pain. Interestingly, mice deficient in COMT, while more sensitive to pain in general, also showed increased pain relief in response to opioids [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561993/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20617305/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18834357/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, most COMT inhibitors increase pain sensitivity in mice and rats. The only exception is </span><em><span style="font-weight: 400;">nitecapone</span></em><span style="font-weight: 400;">, which seems to prevent the activation of certain nerve cells of the spinal cord that perceive pain [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905861/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010567/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/11161631/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Role of Catechol Neurotransmitters</strong></h4> <p><span style="font-weight: 400;">There are several possible mechanisms by which reduced COMT activity may increase pain perception.</span></p> <p><span style="font-weight: 400;">On the one hand, COMT inhibition results in higher norepinephrine and epinephrine levels. These neurotransmitters may increase pain sensitivity by activating receptors in the peripheral nerves. Moreover, the breakdown of these neurotransmitters produces a toxic chemical that may further worsen pain [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905861/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10085337/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746092/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, in certain situations, norepinephrine and epinephrine may also help </span><em><span style="font-weight: 400;">relieve</span></em><span style="font-weight: 400;"> acute pain. For example, one study in rats reported that norepinephrine injections triggered the release of </span><a href="https://selfhacked.com/blog/endorphins/"><span style="font-weight: 400;">endorphins</span></a><span style="font-weight: 400;">, which reduce pain by activating opioid receptors [</span><a href="https://pubmed.ncbi.nlm.nih.gov/15245482/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">On the other hand, reduced COMT activity increases dopamine availability. Although dopamine inhibits pain, it also blocks the production of pain-relieving chemicals (</span><a href="https://selfhacked.com/blog/enkephalins/"><em><span style="font-weight: 400;">enkephalins</span></em></a><span style="font-weight: 400;">) in the brain. On the upside, it can increase the number of opioid receptors in certain brain areas, and may thus enhance the effectiveness of certain opiates [</span><a href="https://pubmed.ncbi.nlm.nih.gov/12595695/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/8101360/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Finally, carriers of underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants showed increased activation of several brain regions responsible for perceiving pain (such as the anterior cingulate cortex, periaqueductal grey, lingual gyrus, cerebellum, hippocampus, and precuneus) in response to painful stimuli [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887789/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221673/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Reduced COMT activity is generally associated with increased pain sensitivity but also better response to opioids. The increased availability of neurotransmitters and activation of pain centers in the brain may account for these effects.</span></p> <h2><strong>Your COMT Results for Pain Sensitivity</strong></h2> <p>*4739259047509141*</p> <p>&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP: </strong><strong><em>COMT </em></strong><strong>rs4680</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Increased pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">41% of the world population has genotype &lsquo;GG&rsquo;&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In people with European ancestry, both alleles are equally frequent</span></li> </ul> <p><strong>Other Important SNPs&nbsp;</strong></p> <p><strong><em>COMT </em></strong><strong>rs6269</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased pain from surgery and sickle cell disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only 14% of the global population has genotype &lsquo;GG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In people with a European background, the &lsquo;A&rsquo; variant is slightly less common</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs4633</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased pain from surgery and sickle cell disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar to that of rs4680 for all ethnicities</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs4818</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased pain from surgery</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Globally, 1 out of 2 people has genotype &lsquo;CC&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The most common situation in European descendants is to carry one copy of each allele</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs165599&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Increased pain from sickle cell disease and experimental (heat) pain</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; allele is only slightly more frequent than &lsquo;A&rsquo; in the global population</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In European descendants, &lsquo;A&rsquo; is the most common allele</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs165774&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Reduced pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only 5% of the world population has genotype &lsquo;AA&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Allele &lsquo;A&rsquo; is slightly more common in people of European ancestry (10% of &lsquo;AA&rsquo;)</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs887200</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Normal pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Reduced pain sensitivity</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Almost 43% of the world population has genotype &lsquo;TT&rsquo;&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In people with a European background, the percentage of &lsquo;TT&rsquo; is increased to 76%</span></li> </ul> <p>*6608694806830928*</p> <p>&nbsp;</p> <h2><strong>Influence of <em>COMT </em>Variants on Pain Perception</strong></h2> <h3><strong>Rs4680</strong></h3> <p><span style="font-weight: 400;">By far, </span><a href="../../../snp/rs4680/"><span style="font-weight: 400;">rs4680</span></a><span style="font-weight: 400;"> is the most widely-studied COMT gene variant. Its minor &lsquo;A&rsquo; allele encodes a less-stable protein that results in reduced COMT levels and activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/7703232/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10581325/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This variant has been associated with increased sensitivity to pain caused by heat and the injection of concentrated </span><a href="https://selfhacked.com/blog/is-salt-good-or-bad-the-science-on-the-health-effects-of-salt/"><span style="font-weight: 400;">salt</span></a><span style="font-weight: 400;"> solution in experiments on healthy people [</span><a href="https://pubmed.ncbi.nlm.nih.gov/12595695/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/16837133/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695541/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study on fibromyalgia patients, carriers of this variant were more sensitive to experimental pain caused by </span><a href="http://selfhacked.com/blog/12-reasons-embrace-cold/"><span style="font-weight: 400;">cold</span></a><span style="font-weight: 400;"> temperatures and pressure [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22528689/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Although the rs4680 polymorphism doesn&rsquo;t influence the risk of chronic </span><a href="https://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">headaches</span></a><span style="font-weight: 400;"> (</span><a href="http://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">migraines</span></a><span style="font-weight: 400;"> and tension headaches), carrying two copies of the &lsquo;A&rsquo; allele results in more severe attacks and increased sensitivity to pressure pain in adults and children [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686934/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30614828/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30481348/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21691248/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;A&rsquo; variant has also been associated with an increased incidence of acute pain crises in people with sickle cell disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205211/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">As previously mentioned, low COMT activity may enhance the effectiveness of opiates. In line with this, people with cancer or postsurgical pain required lower morphine doses when they carried the &lsquo;A&rsquo; variant [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995596/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590034/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25963335/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">A widely-investigated <em>COMT </em>underactive variant is associated with increased sensitivity to painful stimuli.</span></p> <h3><strong>Other Variants</strong></h3> <p><span style="font-weight: 400;">The contribution of the </span><a href="../../../snp/rs6269/"><span style="font-weight: 400;">rs6269</span></a><span style="font-weight: 400;"> polymorphism to COMT activity hasn&rsquo;t been investigated. Its minor &lsquo;G&rsquo; variant is associated with increased pain relief in response to morphine and decreased pain relief in response to butorphanol. This variant is also associated with increased pain from [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31806881/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Surgery (tonsil removal, tooth removal, and orthopedic surgeries) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27792797/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942486/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Sickle cell disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847561/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">The minor &lsquo;T&rsquo; allele of </span><a href="../../../snp/rs4633/"><span style="font-weight: 400;">rs4633</span></a><span style="font-weight: 400;"> increases </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression. This variant is associated with greater pain relief in response to </span><em><span style="font-weight: 400;">butorphanol</span></em><span style="font-weight: 400;">, as well as with increased pain from [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115408/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152328/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31806881/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Surgery (tonsil removal, orthopedic surgery, and groin hernia repair) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942486/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25599448/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Sickle cell disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856032/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">The minor &lsquo;G&rsquo; variant of </span><a href="../../../snp/rs4818/"><span style="font-weight: 400;">rs4818</span></a><span style="font-weight: 400;"> encodes a protein with reduced activity, and has been associated with increased pain after the surgical removal of the uterus and tonsils [</span><a href="https://pubmed.ncbi.nlm.nih.gov/19699472/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25963335/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;A&rsquo; allele of </span><a href="../../../snp/rs165599/"><span style="font-weight: 400;">rs165599</span></a><span style="font-weight: 400;"> reduces </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression in the brain. This variant has been associated with an increased number of severe episodes of pain in people with sickle cell disease and reduced the placebo effect of a fake TENS treatment, resulting in increased sensitivity to pain caused by heat [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180576/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856032/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31661578/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;A&rsquo; allele of </span><a href="../../../snp/rs165774/"><span style="font-weight: 400;">rs165774</span></a><span style="font-weight: 400;"> increases </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">gene expression, but encodes a COMT protein with reduced activity. This variant has been associated with reduced sensitivity to pain from heat and electric stimuli, possibly by increasing dopamine levels [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748386/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869072/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/29550002/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another minor variant, &lsquo;C&rsquo; at rs887200, has been reported to reduce sensitivity to pain caused by cold temperatures [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869072/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Several <em>COMT </em>variants may increase or reduce pain sensitivity.</span></p> <h2><strong>Recommendations to Reduce Pain</strong></h2> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*2982873076439309*</p> <p>&nbsp;</p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Reducing Stress</strong></h4> <p><span style="font-weight: 400;">As previously described, people with under-active </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants (sometimes called &ldquo;</span><a href="https://selfhacked.com/blog/worrier-warrior-explaining-rs4680comt-v158m-gene/"><span style="font-weight: 400;">worriers</span></a><span style="font-weight: 400;">&rdquo;) have excessive levels of norepinephrine and epinephrine in response to </span><a href="https://selfhacked.com/blog/factors-counteract-stress-response/"><span style="font-weight: 400;">stress</span></a><span style="font-weight: 400;">. This reduces their ability to adapt to stressful situations. As previously discussed, these neurotransmitters often also increase pain perception [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17008817/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">In a study, stress increased the risk of developing temporomandibular joint disorder only in people carrying the combination of two underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants (at rs6269 and rs4633) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547321/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, excessive stress has the potential to overload catecholamine activity and reduce the contribution of </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants to stress-induced pain. In a study, the combination of four underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants (at rs4680, rs4818, rs6269, and rs4633) was only associated with increased pain in un-stressed people [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794347/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Genetically-engineered mice lacking </span><em><span style="font-weight: 400;">COMT</span></em><span style="font-weight: 400;"> were especially susceptible to pain triggered by stress. In the study, the effect was even stronger in female mice [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31972854/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Therefore, if you carry this genotype, we recommend addressing sources of stress in your life &mdash; such as by taking up a stress-busting hobby (like </span><a href="https://selfhacked.com/blog/health-benefits-yoga/"><span style="font-weight: 400;">yoga</span></a><span style="font-weight: 400;"> or </span><a href="https://selfhacked.com/blog/meditation/"><span style="font-weight: 400;">meditation</span></a><span style="font-weight: 400;">), or seeking professional help.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">People with underactive <em>COMT</em> variants have reduced ability to cope with stress. Some genotypes may influence the effect of stress on pain perception.</span></p> <h4><strong>Acupuncture</strong></h4> <p><span style="font-weight: 400;">Perhaps the most common use of </span><a href="https://selfhacked.com/blog/acupuncture-benefits-mechanisms-risks/"><span style="font-weight: 400;">acupuncture</span></a><span style="font-weight: 400;"> is to manage chronic pain. Acupuncture is claimed to be effective at pain relief without the side effects of opiates and may even help patients wean off from these drugs [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036643/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27475042"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296192/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Stimulation of acupoints is believed to release </span><a href="https://selfhacked.com/blog/endorphins/"><span style="font-weight: 400;">endorphins</span></a><span style="font-weight: 400;"> and natural </span><a href="https://selfhacked.com/blog/why-the-ice-bucket-challenge-is-so-popular-it-functions-like-heroin/"><span style="font-weight: 400;">opioids</span></a><span style="font-weight: 400;"> in the body, thus reducing the perception of pain. In addition, it may also reduce </span><a href="https://selfhacked.com/blog/63-factors-raising-stress-cortisol-level-backed-science/"><span style="font-weight: 400;">stress</span></a><span style="font-weight: 400;"> and tension. Although meta-analyses generally conclude that this technique provides better pain relief than placebo, a lot of the included studies are of low quality [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26896946"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26896946"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927830/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158087/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28438274/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a small trial on 38 women who developed joint pain from hormonal therapy for breast cancer, those with two copies of the &lsquo;A&rsquo; variant at rs4680 experienced greater pain relief from acupuncture [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329437/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, acupuncture relieved the increased pain sensitivity and nerve inflammation resulting from the altered catecholamine neurotransmission in mice given a COMT inhibitor for 13 days [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289709/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Acupuncture is a Traditional Chinese Medicine technique often used for managing chronic pain. People with underactive <em>COMT </em>variants may especially benefit from acupuncture.</span></p> <h4><strong>Transcutaneous Electrical Nerve Stimulation (TENS)</strong></h4> <p><span style="font-weight: 400;">A </span><a href="https://selfhacked.com/blog/tens-units/"><span style="font-weight: 400;">TENS</span></a><span style="font-weight: 400;"> unit is a device that stimulates nerves throughout the body by applying an electrical current through the skin. Although some studies found this technique effective at relieving certain types of pain such as migraines, back and shoulder pain, and postsurgical pain, a Cochrane review considered the evidence insufficient to support its use [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446021/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a clinical trial on 75 people with knee osteoarthritis, those with the &lsquo;A&rsquo; variant at rs4680 achieved greater pain reduction from this technique. As previously mentioned, the &lsquo;A&rsquo; variant of rs165599 reduced the placebo effect of &ldquo;sham&rdquo; (fake) TENS treatment [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31661578/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">TENS is a technique that stimulates the nerves by applying an electrical current through the skin. Although its potential to relieve pain management is unclear, a study found that <em>COMT </em>variants may influence its effectiveness.</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>SAM-e</strong></h4> <p><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">SAM-e</span></a><span style="font-weight: 400;">, the primary &ldquo;methyl donor&rdquo; used to activate the COMT enzyme, is classified as a supplement in the US and a prescription drug in some European countries.</span></p> <p><span style="font-weight: 400;">Among other uses, SAM-e has the potential to function as a painkiller. In studies of elderly patients, SAM-e was about as effective as NSAID painkillers, but produced fewer side effects (such as stomach ulcers). SAM-e also reduced functional abdominal pain in children [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772852/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23981407/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">According to a review of 70 clinical trials, SAM-e, </span><a href="http://selfhacked.com/blog/21-proven-science-based-reasons-magnesium-amazing-including-drawbacks/"><span style="font-weight: 400;">magnesium</span></a><span style="font-weight: 400;">, and </span><a href="https://selfhacked.com/blog/carnitine-top-18-science-based-health-effects-carnitine/"><span style="font-weight: 400;">L-</span></a><a href="http://selfhacked.com/blog/top-18-science-based-health-effects-carnitine/"><span style="font-weight: 400;">carnitine</span></a><span style="font-weight: 400;"> showed the best results and the most potential for further research in people with fibromyalgia. In a clinical trial on 44 patients, SAM-e (800 mg daily for 6 weeks) reduced muscle pain, fatigue, and morning stiffness [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503476/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20192908"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/1925418"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">A review of clinical studies with over 20,000 patients supports the use of SAM-e for osteoarthritis. It has the same effect as commonly-used NSAIDs with fewer side effects. In a Cochrane review of 4 trials and 656 patients, SAM-e moderately improved pain and joint function. However, the authors warned that the quality of most included studies was low [</span><a href="https://pubmed.ncbi.nlm.nih.gov/3318441/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19821403/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">SAM-e is required for COMT activity and has been shown to reduce pain in people with chronic conditions such as fibromyalgia and osteoarthritis.</span></p>
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267 | content_learn_more_4739259047509141_text == Based on the variants we looked at, your COMT gene is associated with somewhat increased pain sensitivity. Reducing stress can help. Keep scrolling to find out more.
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rsIDs = rs165774,rs887200,rs6269,rs4633,rs165599,rs4818,rs4680
rsStatus = rs165774,COMT,chr22,19965038,G,A,,,34,17,HET
rsStatus = rs887200,ARVCF,chr22,19976143,C,T,,,4,34,HET
rsStatus = rs6269,COMT,chr22,19962429,A,G,T,,13,14,HET
rsStatus = rs4633,COMT,chr22,19962712,C,T,,,21,13,HET
rsStatus = rs165599,ARVCF,chr22,19969258,G,A,C,,23,11,HET
rsStatus = rs4818,COMT,chr22,19963684,C,G,T,,18,13,HET
rsStatus = rs4680,COMT,chr22,19963748,G,A,,,19,11,HET
