The minute you go outside on a winter morning or put some mint in your mouth, a tiny molecular sensor in your body comes into action that tells your brain that you are feeling cold.
It is now possible to have the first detailed pictures of this sensor in action and see just how it identifies not only actual cold but also the feeling of cool with menthol, a substance that is a by-product of mint plants. The study will be presented at the 70th Biophysical Society Annual Meeting in San Francisco between February 21-25, 2026.
The experiment dealt with a protein channel, known as TRPM8, which is a sort of microscopic thermometer located within your body, said Hyuk-Joon Lee, a post-doctoral student in the laboratory of Seok-Yong Lee of Duke University. “It is the main sensor that makes your brain know that it is cold. We have long been aware of the fact that this occurs, but we were not aware of the manner in which it occurs. Now we can see it.”
TRPM8 is positioned in the membrane of the sensory neurons that cover the skin, mouth and eyes. It is a thermoreceptor that reacts to low temperatures (approximately 46 deg F to 82 deg F) and opens up permitting ions to enter the cell, which transmits a nerve impulse to the brain. That is also why menthol, eucalyptus, and some other substances have that feeling of cooling.
Lee explained that Menthol is a ruse. It clings to a certain section of the channel and causes it to open as cold temperature would. Thus whilst menthol does not necessarily freeze anything, your body receives the same information as you felt it to be touching ice.
Lee and colleagues used the cryo-electron microscopy method, a microscopy which freezes the proteins using a flash-freezing technique and surrounds them with an electron beam, to obtain several snapshots of TRPM8 in the closed and open phases.
Cold Causes Pore-Related Changes
They found out that the channel is activator by cold and menthol via identical but different allosteric networks: cold mainly causes pore-related (the part of the channel that opens and admits ions in) changes, whereas menthol binds to a different part of the protein and shifts the shape which spreads to the pore.
Lee said that when menthol was added with cold, the response was synergized. This combo was made to record the channel in its open state, which cold alone had not managed to accomplish.
The medical implications of the findings are medical. The failure to work properly of TRPM8 has been associated with such conditions as chronic pain, migraines,, dry eye and some types of cancers.
Menthol Binds Protein, Shifts Shape Relieving Pain
Acoltremon, which is an activator of TRPM8, is an eye drop used in the treatment of dry eye disease approved by the FDA. It is a menthol analogue, which acts by triggering the cooling pathway to aid in the production of tears and soot irritated eyes.
The researchers managed to find what they term a cold spot a particular area of the protein which is particularly significant in sensing temperature and which aid in preventing desensitization of the channel through extended cold exposure.
Lee said that how cold activates this channel, structurally speaking, had been a mystery before. Now we are able to observe that cold induces certain structural changes in the pore area. This provides us with a basis of designing new treatments that are aimed at attacking this pathway.
The paper provides the original molecular definition of the integration of cold and chemical stimuli to form the sensation of coolness- solving one of the core questions of sensory biology that has plagued scientists over decades.
Recommended FAQs for You:
1. What is the body’s cold sensor and how was it discovered through molecular snapshots?
The cold sensor in our body is a protein called TRPM8 that picks up on chilly temperatures and substances like menthol. Scientists uncovered its workings using cryo-electron microscopy, which snaps detailed atomic images showing how the protein shifts from a closed to an open form when exposed to cold.
2. How does the cold sensor function in the human body?
This sensor operates in nerve cells found in the skin, mouth, and eyes. When temperatures drop below about 25 degrees Celsius or when menthol touches it, the channel opens up, letting calcium ions flow in. This sparks the nerves to send signals to the brain, creating the feeling of cold.
3. In what ways could understanding the cold sensor lead to new treatments for pain?
By figuring out this sensor, researchers can design medications that either block or trigger it to manage ongoing pain issues, like nerve damage sensitivities. This approach might dial down excessive reactions without causing widespread unwanted effects.
4. How might this research impact migraine sufferers?
Issues with this sensor have been tied to migraines. The findings could pave the way for drugs that interrupt cold-related triggers in certain nerves, helping to lessen how often and how badly migraines hit.
5. What is the potential connection between the cold sensor and alleviating dry eye symptoms?
Turning on this sensor in the eye’s nerves can boost tear flow, easing dry eye discomfort. Compounds similar to menthol could activate it to calm irritation and improve moisture, tackling problems where the sensor isn’t working right.
