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SALT LAKE CITY — People react to cold differently. Some love to play in snow and enjoy winter, while others find it literally painful. For some people who are ill, including many cancer patients undergoing chemotherapy, the treatment itself makes them feel excruciatingly cold.
But why cold is experienced so differently has long been a mystery in the field of sensory biology.
Now researchers from the Life Sciences Institute at the University of Michigan and its College of Literature, Science and Art say they've found a protein primarily produced in the brain that's responsible for how mammals sense cold. They theorize the discovery could one day fuel therapeutic targets to help people dramatically impacted by the cold. The study is published in the journal Nature Neuroscience.
In a news release, neuroscientist and study lead author Shawn Xu said that previous studies have found some temperature-sensor proteins, identifying those that tell mammals it's cool, warm or hot. "But we've been unable to confirm what senses temperatures below about 60 degrees Fahrenheit."
His lab was the first to find a cold-sensing receptor, making the discovery in 2019 while studying the C. elegans worm, which shares many genes with mice and other mammals, including humans. C. elegans was being examined for sensory response and it delivered. That discovery "provided a starting point" for verifying the cold sensor in mammals: a protein whose name has been shortened to GluK2 from its more formal name, Glutamate ionotropic receptor kainate type subunit 2.
The protein outside the brain
The release said the protein is most often found on brain neurons, "where it receives chemical signals to facilitate communication between neurons. But it is also expressed in sensory neurons in the peripheral nervous system outside the brain and spinal cord."
From there, the University of Michigan team used mice that did not have the GluK2 gene and could not produce the protein, testing the animals' reaction to temperatures and other stimuli. The response was normal when it came to hot, warm and cool temperatures, but the response was entirely lacking to what they called "noxious cold."
"We now know that this protein serves a totally different function in the peripheral nervous system, processing temperature cues instead of chemical signals to sense cold," said Bo Duan, University of Michigan associate professor of molecular, cellular and developmental biology and co-senior author of the study.
The researchers believe the protein works differently in the brain than in the peripheral nervous system and theorize that temperature sensing "may have been one of its original purposes."
Xu believes this finding could impact human health.
"This discovery of GluK2 as a cold sensor in mammals opens new paths to better understand why humans experience painful reactions to cold and even perhaps offers a potential therapeutic target for treating that pain in patients whose cold sensation is overstimulated," he said.
