283 | id == 283
283 | category_id == 19
283 | category_order == 16
283 | category_name == Pain
283 | category_color == #C47AC0
283 | slug == TRPM8-pain
283 | title == What Does the Cold Sensitivity Gene Have to Do With Migraines? (TRPM8)
283 | meta_description == TRPM8 is a cold receptor that may affect hypersensitivity to pain. Can it be used to reduce the pain of migraines?
283 | summary == <p><strong>TRPM8 is a cold receptor that may affect hypersensitivity to pain. Can it be used to reduce the pain of migraines? Read on to learn more.</strong></p>
283 | overall_score_text == Migraine Score (based on TRPM8)
283 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/TRPM8__Pain_Headaches__Migraine.jpg
283 | author_id == 1
283 | author_name == Jasmine Foster
283 | author_title == BSc, BEd
283 | author_order == 36
283 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
283 | author_intro == <p><strong>Jasmine received her BS from McGill University and her BEd from Vancouver Island University.</strong></p>    <p>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.</p>
283 | reviewer_id == 14
283 | reviewer_name == Shany Lahan
283 | reviewer_title == MS (Neuroscience)
283 | medical_reviewer_id == 11
283 | medical_reviewer_name == Puya Yazdi
283 | medical_reviewer_title == MD
283 | publish_date == 2020
283 | publish_date == 8
283 | publish_date == 21
283 | avg_rating == 5.0
283 | tags_id == 600
283 | tags_name == Capsaicin
283 | tags_id == 188
283 | tags_name == Cold Resistance
283 | tags_id == 633
283 | tags_name == Cold Sensitivity
283 | tags_id == 69
283 | tags_name == Headache
283 | tags_id == 31
283 | tags_name == Migraine
283 | tags_id == 71
283 | tags_name == Pain
283 | tags_id == 399
283 | tags_name == TRPM8 Gene
283 | permissions_favorite == False
283 | permissions_rate == False
283 | 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><span style="font-weight: 400;">What is TRPM8?</span></h2> <p><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">TRPM8 </span></em><span style="font-weight: 400;">gene encodes the major sensory receptor of cold in our bodies. It is activated either by cold temperatures or by menthol (the active compound in peppermint), which is why mint makes our mouths feel cold [</span><a href="https://www.ncbi.nlm.nih.gov/books/NBK5238/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">TRPM8 becomes less sensitive in the presence of acidic pH and more sensitive in the presence of menthol [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574235"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220012"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This cold receptor plays a complex role in </span><a href="https://selfhacked.com/blog/23-ways-to-combat-pain-naturally-by-increasing-your-opioids/"><span style="font-weight: 400;">pain</span></a><span style="font-weight: 400;"> perception. In &ldquo;hot&rdquo; or burning pain, the heat receptor </span><a href="https://www.selfdecode.com/gene/trpv1/"><span style="font-weight: 400;">TRPV1</span></a><span style="font-weight: 400;"> is activated and TRPM8 (which would produce a cooling sensation) is blocked. However, TRPM8 can also be sensitized to produce &ldquo;cold&rdquo; pain [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574235"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220012"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Adaptation to Climate</span></h3> <p><span style="font-weight: 400;">While a lot of genes show variation between different populations of people, </span><em><span style="font-weight: 400;">TRPM8 </span></em><span style="font-weight: 400;">is especially dramatic. A variant that increases </span><em><span style="font-weight: 400;">TRPM8 </span></em><span style="font-weight: 400;">expression is much more common in Northern Europeans than in Africans: 88% in Finland compared with 5% in Nigeria [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933706/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]!</span></p> <p><span style="font-weight: 400;">TRPM8 makes us more sensitive to cold sensations. One might think that reduced cold sensitivity would be an advantage for people living in cold climates, so it may seem strange that northern populations have increased TRPM8 expression. However, increased sensitivity to cold may cause increased production of body heat, among other adaptations [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927963/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Unfortunate Side Effects</span></h3> <p><span style="font-weight: 400;">People with a higher amount of TRPM8 might have an advantage in colder climates, but they&rsquo;re also more susceptible to certain types of pain disorders. Most notably, the high-expression variant rs10166942-T is associated with IBS and </span><a href="http://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">migraines</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933706/"><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;"><span style="font-weight: 400;">TRPM8 is activated by both cold temperatures and menthol, the active compound in peppermint. People in colder climates tend to have higher expression of </span><em><span style="font-weight: 400;">TRPM8</span></em><span style="font-weight: 400;">.</span></span></p> <h2><span style="font-weight: 400;">How Does TRPM8 Affect Migraines?</span></h2> <p><em><span style="font-weight: 400;">TRPM8</span></em><span style="font-weight: 400;"> has been linked to migraines, but researchers haven&rsquo;t completely nailed down how the connection might work. One possibility, emerging from a rodent study, is that the TRPM8 receptor can interact with a type of </span><a href="https://www.selfhacked.com/blog/how-to-increase-serotonin"><span style="font-weight: 400;">serotonin</span></a><span style="font-weight: 400;"> receptor called </span><a href="https://www.selfdecode.com/gene/htr1b/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">5-HT1B</span></a><span style="font-weight: 400;"> and suppress hypersensitivity to pain [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24269608/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Serotonin receptors, in turn, are heavily implicated in migraines. Triptans, a common class of drugs prescribed to treat a migraine in progress, work by binding to the serotonin receptors 5-HT1B and 5-HT1D. Once activated, these receptors constrict the blood vessels in the brain, counteracting the painful widening of these vessels during a migraine attack [</span><a href="https://www.ncbi.nlm.nih.gov/books/NBK554507/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3452288/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Thus, TRPM8 might work like a kind of natural triptan, encouraging blood vessels to constrict and preventing hypersensitivity to pain. However, some evidence seems to suggest that increased </span><em><span style="font-weight: 400;">TRPM8</span></em><span style="font-weight: 400;"> expression is linked to increased susceptibility to migraines, so the direction of effect isn&rsquo;t clear [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24269608/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/books/NBK554507/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3452288/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">TRPM8 interacts with a type of serotonin receptor, 5-HT1B, which constricts the blood vessels and prevents hypersensitivity to pain. Scientists suspect that this mechanism could be behind TRPM8&rsquo;s link to migraines.</span></p> <h2><span style="font-weight: 400;">TRPM8 Variants &amp; Migraine</span></h2> <p><span style="font-weight: 400;">Three variants of </span><em><span style="font-weight: 400;">TRPM8</span></em><span style="font-weight: 400;"> have been associated with migraines, and one has been linked to how well a migraine patient responds to triptan medications.</span></p> <h3><span style="font-weight: 400;">Migraine Incidence</span></h3> <p><span style="font-weight: 400;">The three variants of </span><em><span style="font-weight: 400;">TRPM8 </span></em><span style="font-weight: 400;">associated with the presence or absence of migraine are </span><a href="../../../snp/rs10166942/"><span style="font-weight: 400;">rs10166942</span></a><span style="font-weight: 400;">, </span><a href="../../../snp/rs7577262/"><span style="font-weight: 400;">rs7577262</span></a><span style="font-weight: 400;">, and </span><a href="../../../snp/rs17862920/"><span style="font-weight: 400;">rs17862920</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125402/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031047/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773912/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The best-studied of these is rs10166942, at which each copy of the minor &lsquo;T&rsquo; allele is associated with a greater incidence of chronic migraines. People with one copy of the &lsquo;T&rsquo; allele tend to have migraines more often than those without a &lsquo;T&rsquo; allele, and those with two copies (the &lsquo;TT&rsquo; genotype) tend to have migraines more often than those with one [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125402/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916225/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28952330/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773912/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331903/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">At rs7577262, the minor &lsquo;A&rsquo; allele may be somewhat protective against migraine. Two studies have found that the &lsquo;A&rsquo; allele is less common in people who experience migraines than in people who don&rsquo;t [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031047/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041123/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Finally, the minor &lsquo;T&rsquo; allele of rs17862920 may also be somewhat protective against migraine [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773912/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Response to Migraine Medication</span></h3> <p><span style="font-weight: 400;">At least one study has found a link between a </span><em><span style="font-weight: 400;">TRPM8</span></em><span style="font-weight: 400;"> variant and how well a migraine patient responds to triptans. At rs6724624, the &lsquo;G&rsquo; allele was associated with an inconsistent triptan response [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30256423/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The researchers cautioned that the link between rs6724624-G and triptan response might not be statistically significant. They also noted, however, that it was worth another look, given how </span><em><span style="font-weight: 400;">TRPM8 </span></em><span style="font-weight: 400;">seems to be involved in migraine more broadly [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30256423/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The rs6724624 and rs10166942 variants appear to be inherited together. You can use the table below to see which rs6724624 alleles you are likely to carry based on the one you have atrs10166942.</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;"><span style="font-weight: 400;">Variants of the </span><em><span style="font-weight: 400;">TRPM8</span></em><span style="font-weight: 400;"> gene have been associated with the incidence of migraine and with how well a migraine patient responds to triptans.</span></span></p> <h2><span style="font-weight: 400;">Your TRPM8 Results for Migraine</span></h2> <p>*8375268358460197*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>TRPM8 rs10166942</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Not associated with migraines</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with increased incidence of migraines</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 29% of all people worldwide carry the &lsquo;TT&rsquo; genotype.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;TT&rsquo; genotype is much more common in people of European (69%) and American (51%) descent and almost nonexistent in people of African descent (1.5%).</span></li> </ul> <p><strong>TRPM8 rs7577262</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Not associated with migraines&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Possibly protective against migraines</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 40% of all people worldwide carry at least one copy of the &lsquo;A&rsquo; allele.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;A&rsquo; allele is significantly less common in people of European (17%) and American (16%) descent and more common in people of East Asian descent (64%).</span></li> </ul> <p><strong>TRPM8 rs17862920</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Not associated with migraines</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Possibly protective against migraines</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 26% of all people worldwide carry at least one copy of the &lsquo;T&rsquo; allele.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;T&rsquo; allele is significantly more common in people of East Asian (49%) and South Asian (41%) descent.</span></li> </ul> <p><strong>TRPM8 rs6724624</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Less consistent response to triptans</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = More consistently successful response to triptans</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 29% of all people worldwide carry the &lsquo;CC&rsquo; genotype.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;CC&rsquo; genotype is much more common in people of European (69%) and American (51%) descent and almost nonexistent in people of African descent (1.5%).</span></li> </ul> <p>*2984483114164937*</p> <h2><span style="font-weight: 400;">Recommendations for Preventing Migraines</span></h2> <p>*6397553287965405*</p> <h3><span style="font-weight: 400;">Apply Menthol</span></h3> <p><span style="font-weight: 400;">High expression of the </span><em><span style="font-weight: 400;">TRPM8 </span></em><span style="font-weight: 400;">gene and high activation of the TRPM8 receptor may be associated with migraine in some people. The most obvious genetic &ldquo;solution&rdquo; would then be to either decrease or block TRPM8 and to avoid any compounds, such as menthol, that activate it. However, researchers have suggested that menthol can also desensitize TRPM8 over time [</span><a href="https://pubmed.ncbi.nlm.nih.gov/23963768/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Applying menthol to the skin may help reduce the symptoms of a migraine in progress, but only in migraines without aura. Depending on your specific genes and type of migraine, menthol might be more helpful over the course of several days or weeks (as it desensitizes TRPM8) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20456191/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Apply Gentle Heat</span></h3> <p><span style="font-weight: 400;">TRPM8 is activated by cold temperatures and suppressed by heat. Applying warmth to the skin using hot water bottles or heating pads may help block TRPM8 activation [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752590/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Hot showers and other gentle applications of heat are often recommended for tension </span><a href="https://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">headaches</span></a><span style="font-weight: 400;">. However, heat can be a trigger for some migraineurs, so it&rsquo;s important to be aware of your body&rsquo;s responses to changes in temperature. If you have a lot of TRPM8 receptors, heat may be helpful [</span><a href="https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Headache-Hope-Through-Research"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082953/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">Apply Capsaicin</span></h3> <p><a href="http://selfhacked.com/blog/capsaicin/"><span style="font-weight: 400;">Capsaicin</span></a><span style="font-weight: 400;"> is the compound that makes chilli peppers hot. Capsaicin activates the heat receptor TRPV1 and blocks TRPM8; this activity leads to the hot feeling we get when we eat spicy foods [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752590/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Applied through the nose, capsaicin reduced the number and severity of cluster </span><a href="https://selfhacked.com/blog/natural-treatment-migraines/"><span style="font-weight: 400;">headache</span></a><span style="font-weight: 400;"> attacks in 3 small trials on 89 people. Though the initial experience is quite painful, the capsaicin appeared to desensitize pain-sensing nerves [</span><a href="https://pubmed.ncbi.nlm.nih.gov/2520386/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/7708405/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/8495452/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some research suggests that applying a jelly containing capsaicin to the skin can help reduce the pain of migraine. In one study of 23 migraine patients, the best results were observed&nbsp; after applying the jelly in between migraines [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20456192/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The sensitivity of TRPM8 can be modified with gentle heat, menthol, and capsaicin. However, individuals may respond very differently to these strategies; we recommend talking to your doctor before trying them.</span></p>
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283 | content_learn_more_2984483114164937_text == Based on the variants we looked at, your TRPM8 gene is somewhat associated with migraines. However, this doesn't necessarily reflect your overall risk of migraines, just one gene related to it. Applying gentle heat, menthol, or capsaicin to the skin may help. Keep scrolling to find out more.
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rsIDs = rs6724624,rs7577262,rs17862920,rs10166942
rsStatus = rs6724624,,chr2,233911933,C,G,,,10,10,HET
rsStatus = rs7577262,,chr2,233910224,G,A,T,,38,0,Normal
rsStatus = rs17862920,TRPM8,chr2,233919350,C,T,,,31,0,Normal
rsStatus = rs10166942,TRPM8,chr2,233916448,T,A,C,,29,0,Normal
