gut health

TRPM8

A Link Between Cold Perception & Gut Pain? (TRPM8)

Written by Jasmine Foster, BSc, BEd on May 1st, 2020

TRPM8 is a cold-sensitivity gene that affects the way our bodies perceive and respond to temperature. What is its role in IBS? Read on to learn more.

What is TRPM8?

TRPM8 is the major sensory perceptor of cold in our bodies. It is activated either by cold temperatures or by menthol, which is why mint makes our mouths feel cold [R].

TRPM8 becomes less sensitive in the presence of acidic pH and more sensitive in the presence of menthol [R, R].

This cold receptor plays a complex role in pain perception. In “hot” or burning pain, the heat receptor TRPV1 is activated and TRPM8 (which would produce a cooling sensation) is blocked. However, TRPM8 can also be sensitized to produce “cold” pain [R, R].

Adaptation to Climate

While a lot of genes show variation between different populations of people, TRPM8 is especially dramatic. A variant that increases TRPM8 expression is much more common in Northern Europeans than in Africans: 88% in Finland compared with 5% in Nigeria [R]!

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 [R].

Unfortunate Side Effects

People with higher TRPM8 might have had an advantage in colder climates, but they’re also more susceptible to certain types of pain disorders. Most notably, the high-expression variant rs10166942-T is associated with migraines and with IBS [R].

TRPM8 senses cold temperatures and is activated by both cold and menthol, the active compound in peppermint. People in colder climates tend to have higher expression of TRPM8.

TRPM8 & IBS

The main TRPM8 variant associated with IBS is rs10166942. At this SNP, the ‘T’ allele appears to increase expression of TRPM8 and increase sensitivity to changes in cold temperature and to menthol. The ‘C’ allele, by contrast, is linked to relatively lower TRPM8 expression and reduced sensitivity to changes in cold temperature [R].

The ‘T’ allele of this SNP is likewise associated with increased rates of constipation-predominant IBS (IBS-C) and mixed IBS (IBS-M). Researchers don’t know for sure why TRPM8 is linked to IBS; however, most think it has something to do with this receptor’s role in pain perception [R].

People with IBS often have something called visceral hypersensitivity; that is, their guts are more sensitive to internal pain triggers [R].

The ‘T’ allele of rs10166942 is associated with increased expression of TRPM8 and increased rates of IBS-C and IBS-M.

Your TRPM8 Results for Gut Inflammation

SNP Table

variant	genotype	frequency	risk allele
rs10166942

SNP Summary and Table

TRPM8 rs10166942

‘C’ = Lower expression of TRPM8, less sensitivity to cold, no association with IBS
‘T’ = Higher expression of TRPM8, more sensitivity to cold, potential predisposition to IBS

Recommendations

Applying Heat

TRPM8 is activated by cold temperatures and suppressed by heat. Applying warmth to the abdomen using hot water bottles or heating pads may help block TRPM8 activation [R].

Heating pads are a popular anecdotal remedy for IBS, but there is very little conventional research on their effect. If they work for you and you have high TRPM8 expression, it may have something to do with your cold receptors!

Peppermint & Menthol

High expression and activation of TRPM8 is associated with IBS-C and IBS-M. The most obvious genetic “solution” 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 [R].

Peppermint, which is rich in menthol, is a traditional remedy for digestive distress, and some research suggests that it may help reduce the symptoms of IBS [R, R, R, R].

If your doctor determines that peppermint may help in your case, you may want to try it as a daily supplement. If you have high TRPM8 expression, it is possible that peppermint could initially activate these receptors and desensitize them over the course of days or weeks.

Spicy Foods & Capsaicin

Capsaicin activates the heat receptor TRPV1 and blocks TRPM8; this activity leads to the hot feeling we get when we eat spicy foods [R].

Spicy foods may be a trigger for some people with IBS. For others, however, the capsaicin in spicy foods may actually help reduce IBS symptoms. One study found that six-week supplementation with a red pepper powder containing capsaicin significantly reduced abdominal pain and bloating in 50 IBS patients [R, R].

This is another strategy that may work very well for some people with high TRPM8 and not at all for others. If spicy foods are not a trigger for your IBS, you may want to test out how well you tolerate them and whether they might even help!

If you do not enjoy spicy food and want to test out these effects, red pepper (capsicum) extracts are available as supplements.

TRPM8 can be blocked with heat and spicy foods, while extended exposure to menthol (peppermint) may desensitize it. Individual people with IBS may have wildly different responses to these stimuli; your doctor can help you determine whether it’s worth giving them a try.

Drugs

Researchers are currently developing TRPM8-blocking drugs that may help with specific types of pain. One of these is 5-benzyloxytryptamine (5-BT), a member of the tryptamine family and structurally similar to many migraine medications. In addition to blocking TRPM8, 5-BT activates serotonin receptors [R, R].

TRPM8 antagonists are relatively poorly researched and should never be taken without the careful direction of a doctor.

Jasmine Foster

BSc, BEd

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

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

Disclaimer

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

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

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

More gut health blogs

Could This Gene Be Linked To Gut Inflammation? (ATG16L1) Could This Gene Play A Role In Inflammatory Bowel Disease? (STAT3) How Do Your Genes Respond to Dietary Fat? (TCF7L2) Do Your Genes Favor the Mediterranean Diet? (TCF7L2) How Does this Serotonin Receptor Affect Gut Inflammation? (HTR3E) The Impact of a Serotonin Receptor on IBS-D (HTR3A) How Can Neurotrophins Affect Gut Inflammation? (BDNF) Could Your IBS Symptoms Be Caused by an Enzyme Deficiency? (SI) What is the Connection Between β-Klotho and Gut Inflammation? (KLB) Can This Gene Worsen Gut Inflammation? (NOS2)

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What is TRPM8? TRPM8 & IBS Your TRPM8 Results for Gut Inflammation

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