265 | id == 265
265 | category_id == 19
265 | category_order == 16
265 | category_name == Pain
265 | category_color == #C47AC0
265 | slug == COMT-chronic-pain
265 | title == Can This Gene Make You Prone to Chronic Pain (COMT)?
265 | meta_description == COMT breaks down neurotransmitters and is associated with chronic pain. Learn more here.
265 | 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 are associated with chronic pain. Read on to learn where your COMT gene stands.&nbsp;</strong></p>
265 | overall_score_text == Your Chronic Pain Score (based on COMT Gene)
265 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/COMT--Pain.jpg
265 | author_id == 12
265 | author_name == Carlos Tello
265 | author_title == PhD
265 | author_order == 55
265 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
265 | 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>
265 | author_social_media_name == linkedin
265 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
265 | author_social_order == 1
265 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
265 | reviewer_id == 14
265 | reviewer_name == Shany Lahan
265 | reviewer_title == MS (Neuroscience)
265 | medical_reviewer_id == 11
265 | medical_reviewer_name == Puya Yazdi
265 | medical_reviewer_title == MD
265 | publish_date == 2020
265 | publish_date == 8
265 | publish_date == 11
265 | avg_rating == 5.0
265 | tags_id == 596
265 | tags_name == Chronic Pain
265 | tags_id == 65
265 | tags_name == COMT Gene
265 | tags_id == 51
265 | tags_name == Dopamine
265 | tags_id == 53
265 | tags_name == Epinephrine
265 | tags_id == 7
265 | tags_name == Fibromyalgia
265 | tags_id == 52
265 | tags_name == Norepinephrine
265 | tags_id == 598
265 | tags_name == Opioids
265 | tags_id == 597
265 | tags_name == Temporomandibular Joint Disorders
265 | permissions_favorite == False
265 | permissions_rate == False
265 | content_article == <p><span style="font-weight: 400;"><em>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.</em></span></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 the methyl donor. Having too little SAM-e or too much S-adenosylhomocysteine (SAH) &mdash; formed when SAM-e loses its methyl group &mdash; results in COMT inhibition [</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 catecholamines, 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, 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>Catechol Neurotransmitters and Pain</strong></h3> <p><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants with reduced activity have been associated with different chronic pain conditions. The role of COMT in catecholamine neurotransmission seems to account for these effects [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22722321/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">On the one hand, COMT inhibition results in higher norepinephrine and epinephrine levels. These neurotransmitters can increase pain sensitivity by activating receptors in the peripheral nerves, which causes inflammation. Moreover, their breakdown produces a toxic chemical that worsens 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/PMC6129429/"><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, norepinephrine and epinephrine may also relieve acute pain. A study in rats showed 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, a reduced COMT activity increases dopamine availability. Although dopamine inhibits pain, sustained activation of its receptors by excessive availability of this neurotransmitter blocks further dopamine release. As a result, pain sensitivity is increased [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357127/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">High dopamine levels also influence opioid neurotransmission. A study on healthy volunteers found that those with an underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variant had decreased activation of opioid receptors in response to pain. In line with this, synthetic dopamine reduced the production of the opioid enkephalin in mice [</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;">On the upside, low COMT activity also increases the number of opioid receptors in certain brain areas. This may account for the increased pain relief in response to opioids often observed in people with underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants [</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/16040257/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22722321/"><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://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://pubmed.ncbi.nlm.nih.gov/29402857/"><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 but also better response to opioids. The increased availability of norepinephrine, epinephrine, and dopamine account for these effects.</span></p> <h2><strong>Your COMT Results for Chronic Pain</strong></h2> <p>*1450030790330823*</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 risk of chronic pain</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Increased risk of fibromyalgia and other chronic conditions</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">41% of the world population only carries the &lsquo;G&rsquo; allele</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>rs4818</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of chronic pain</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased risk of chronic postsurgical pain, fibromyalgia, and temporomandibular joint disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Globally, 1 out of 2 people only carries the &lsquo;C&rsquo; variant</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">It is most common in European descendants to carry one copy of each allele</span></li> </ul> <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 risk of chronic pain</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased risk of fibromyalgia and temporomandibular joint disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only 14% of the global population has &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>rs5993882&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Normal risk of chronic pain</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased pain from temporomandibular joint disorder</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Worldwide, only 7% of the population has &lsquo;GG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar in the case of European descendants</span></li> </ul> <p>*7451132115189338*</p> <p>&nbsp;</p> <h2><strong>Influence of <em>COMT </em>Variants on Chronic Pain</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 polymorphism . Its minor &lsquo;A&rsquo; variant 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;">Fibromyalgia is a chronic condition characterized by widespread pain and fatigue. The &lsquo;A&rsquo; variant has been associated with this disorder in most studies. Some of them also associated it with increased psychological distress and worse coping with the condition. A meta-analysis of 5 studies concluded that this variant is linked to an increased incidence and severity of fibromyalgia, except in European and Turkish populations [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20074440/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21120493/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">; </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390547/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24342707/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21125150/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23025981/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21895373/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053137/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24951880/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, this variant has been associated with worse pain, increased disability, and slower recovery in people with chronic sciatica and other forms of lower-back pain. However, carrying the &lsquo;GG&rsquo; genotype at this polymorphism predicted an increased risk of progression from transient to chronic back pain [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22337560/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25772090/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31269327/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211115/"><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 increased incidence or severity of the following chronic conditions:</span></p> <ul> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/causes-symptoms-diagnosis-risk-factors-of-multiple-sclerosis/"><span style="font-weight: 400;">Multiple sclerosis</span></a><span style="font-weight: 400;"> [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24290452/"><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;">Carpal tunnel syndrome [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24077209/"><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;">Temporomandibular joint disorders [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31490699/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">However, this polymorphism doesn&rsquo;t contribute equally to all types of pain. In conditions such as Parkinson&rsquo;s disease and osteoarthritis, &lsquo;G&rsquo; seems to be the variant associated with increased pain [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524945/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548933/"><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 COMT underactive variant is associated with pain from some chronic conditions, especially fibromyalgia and low-back pain.</span></p> <h3><strong>Other Variants</strong></h3> <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 is associated with chronic pain from [</span><a href="https://pubmed.ncbi.nlm.nih.gov/19699472/"><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 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898361/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31206175/"><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;">Fibromyalgia [</span><a href="https://pubmed.ncbi.nlm.nih.gov/21120493/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26849490/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390547/"><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;">Temporomandibular joint disorders [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30811655/"><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/rs6269/"><span style="font-weight: 400;">rs6269</span></a><span style="font-weight: 400;"> has also been associated with fibromyalgia and temporomandibular joint disorders, but its contribution to COMT activity hasn&rsquo;t been investigated [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30811655/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354525/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390547/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;G&rsquo; allele of </span><a href="../../../snp/rs5993882/"><span style="font-weight: 400;">rs5993882</span></a><span style="font-weight: 400;"> is associated with temporomandibular joint pain [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22337325/"><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;">Some COMT polymorphisms have been associated with increased risk and pain severity of chronic conditions such as fibromyalgia and temporomandibular joint disorders.</span></p> <h2><strong>Recommendations to Reduce Pain</strong></h2> <p><span style="font-weight: 400;"><em>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.</em></span></p> <p>*6702854376158029*</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 underactive </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 and often increases 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 </span><a href="../../../snp/rs4633/"><span style="font-weight: 400;">rs4633</span></a><span style="font-weight: 400;">) [</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;">Engineered mice lacking COMT were especially susceptible to pain triggered by chronic stress. In the study, the effect was 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;">We recommend addressing sources of stress in your life, either 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 COMT variants have reduced ability to cope with stress. Some genotypes may influence the effect of stress on pain development.</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 typically used in chronic pain management. 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. Surprisingly, another variant (&lsquo;G&rsquo; at </span><a href="../../../snp/rs165599/"><span style="font-weight: 400;">rs165599</span></a><span style="font-weight: 400;">) enhanced the placebo effect of sham (&ldquo;fake&rdquo;) 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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265 | content_learn_more_1450030790330823_text == Based on the variants we looked at, your COMT gene is associated with somewhat increased risk and severity of chronic pain conditions. Reducing stress can help. Keep scrolling to find out more.
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rsIDs = rs6269,rs5993882,rs4633,rs165599,rs4818,rs4680
rsStatus = rs6269,COMT,chr22,19962429,A,G,T,,13,14,HET
rsStatus = rs5993882,COMT,chr22,19950010,T,C,G,,23,0,Normal
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
