How do we feel the cold?

New breakthrough in sensory biology
20 March 2024


Pile of ice-cubes


A protein called GluK2 acts like a small sensor in our bodies that helps us feel cold temperatures, scientists say...

“We have identified proteins that can detect cool, warm and hot temperatures,” said Wenwen Zhang, co-author of the study. “However, little is known about the protein that can specifically detect cold temperatures, below 15°C.”

Back in 2019, a study in C.elegans, a species of millimetre-long worms, identified a cold-sensitive protein called GluK2. What was interesting about this protein was that it is also found in mice and humans.

To find out what it might be doing for us, and mice, scientists at University of Michigan, set about deleting the gene that codes for the GluK2 protein in mice.

“We knocked out the GluK2 gene in mice and detected how different temperature controls behaviour. We found that, while GluK2 mice respond normally to mechanical and heat stimuli, they exhibit a specific deficit in sensing cold rather than cool temperatures,” explains Zhang.

But how does GluK2 sense cold temperatures?

The team found that the protein is not only active in the brain, where the idea was that it was involved in sending signals between neurons, but in the peripheral nervous system too. This is the network of nerves outside the brain and spinal cord.

And mice missing GluK2 in their peripheral nerves were unable to process temperature signals or react to them. This tells us that GluK2 is not only responsible for helping us to think, but it also helps us feel things, specifically cold temperatures.

The team hypothesised that it’s possible that temperature-sensing was the original purpose of the GluK2 protein. They found relatives of the protein dating back to single-celled organisms such as bacteria, which have been since the time when life first began on Earth.

As bacteria lack a brain, scientists deduce that they used proteins like GluK2 to sense the environment around them, including the temperature and the concentrations of different chemicals. Over evolutionary time the functions of the proteins have been adapted as more complex lifeforms appeared.

So what does this all mean for us? Apart from adding a new piece to the temperature-sensing puzzle, this finding also helps us understand how and why people perceive temperature differently.

“Exposure to cold, particularly chronic cold, can cause tissue damage and invoke pain. Cold-induced pain represents a severe health condition and currently there’s no effective cure for cold pain. Our studies identify GluK2 as a new drug target for developing therapeutics for treating cold pain,” Zhang explains.