Scientists Reveal How Body Senses Cold, Menthol's Chill

Researchers capture first detailed images of TRPM8 protein channel that detects temperature and triggers nerve signals to the brain.

Feb. 22, 2026 at 12:16am

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Scientists have captured the first detailed images of the TRPM8 protein channel, which is the primary sensor that tells the brain when it's cold. The research reveals how TRPM8 responds to both actual cold temperatures and the perceived coolness of menthol, providing new insights into the molecular mechanisms behind the sensation of coldness.

Why it matters

Understanding how the body senses cold and menthol at the molecular level has important medical implications, as TRPM8 dysfunction has been linked to chronic pain, migraines, dry eye, and certain cancers. This knowledge could lead to the development of new treatments targeting the TRPM8 pathway.

The details

The study focused on the TRPM8 protein channel, which sits in the membranes of sensory neurons and responds to cold temperatures between 46°F and 82°F by opening up and allowing ions to flow into the cell, triggering a nerve signal to the brain. TRPM8 also responds to menthol, eucalyptus, and other compounds that produce a cooling sensation, even though they aren't actually cold. Using cryo-electron microscopy, the researchers captured multiple conformational snapshots of TRPM8 as it transitions from closed to open, revealing that cold and menthol activate the channel through shared yet distinct mechanisms.

  • The research will be presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21–25, 2026.

The players

Hyuk-Joon Lee

A postdoctoral fellow from Seok-Yong Lee's laboratory at Duke University who led the study.

Seok-Yong Lee

The laboratory director at Duke University where the research was conducted.

TRPM8

A protein channel that is the primary sensor that tells the brain when it's cold.

Acoltremon

An FDA-approved eye drop for dry eye disease that works by activating the TRPM8 cooling pathway to stimulate tear production and soothe irritated eyes.

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What they’re saying

“Imagine TRPM8 as a microscopic thermometer inside your body. It's the primary sensor that tells your brain when it's cold. We've known for a long time that this happens, but we didn't know how. Now we can see it.”

— Hyuk-Joon Lee, Postdoctoral fellow

“Menthol is like a trick. It attaches to a specific part of the channel and triggers it to open, just like cold temperature would. So even though menthol isn't actually freezing anything, your body gets the same signal as if it were touching ice.”

— Hyuk-Joon Lee, Postdoctoral fellow

“When cold is combined with menthol, the response is enhanced synergistically. We used this combination to capture the channel in its open state—something that hadn't been achieved with cold by itself.”

— Hyuk-Joon Lee, Postdoctoral fellow

What’s next

The researchers also identified a "cold spot" - a specific region of the TRPM8 protein that is uniquely important for sensing temperature and helps prevent the channel from becoming desensitized during prolonged cold exposure. This new understanding of the molecular mechanisms behind cold and menthol sensation could lead to the development of new treatments targeting the TRPM8 pathway.

The takeaway

This research provides the first detailed, molecular-level explanation of how the body senses cold temperatures and the perceived coolness of menthol, solving a long-standing puzzle in sensory biology. The findings have important implications for developing new treatments for conditions linked to TRPM8 dysfunction, such as chronic pain, migraines, and dry eye disease.