Ann Arbor Times

Researchers at the University of Michigan have mapped a complete sensory pathway that shows how the skin relays information about cool temperatures to the brain. The study, published in Nature Communications, suggests that there are dedicated neural circuits for different temperature sensations, with cool and hot each having their own distinct pathways.

Bo Duan, associate professor of molecular, cellular, and developmental biology at the University of Michigan and senior author of the study, explained the significance: “The skin is the body’s largest organ. It helps us detect our environment and separate, distinguish different stimuli. There are still many interesting questions about how it does this, but we now have one pathway for how it senses cool temperatures. This is the first neural circuit for temperature sensation in which the full pathway from the skin to the brain has been clearly identified.”

Duan added that this research advances understanding of basic biology and may help explain how humans evolved to inhabit safe environments while avoiding dangerous extremes. He also pointed out possible medical applications: more than 70% of people who have undergone chemotherapy experience pain triggered by cool temperatures. According to Duan, “The new study found that the neural circuit responsible for sensing innocuous cool does not mediate this type of cold pain. But, in understanding how the cool-sensing circuitry works when it’s functioning properly under normal conditions, researchers now have a better chance of discovering what goes wrong in disease or injury. It could also help develop targeted therapies that restore healthy sensation without impairing normal temperature perception.”

The research was funded by the National Institutes of Health and involved collaboration with Shawn Xu’s team at U-M Life Sciences Institute.

Using advanced imaging techniques and electrophysiology in mice, Duan’s team tracked how signals from skin sensors—responsive to temperatures between 15 and 25 degrees Celsius—are transmitted via primary sensory neurons to specialized interneurons in the spinal cord. These interneurons amplify the signal before projection neurons carry it to the brain.

Duan noted: “These tools have allowed us to identify the neural pathways for chemical itch and mechanical itch previously. Working together, the team identified this very interesting, very dedicated pathway for cool sensation.”

Previous studies had identified molecular thermometers in skin cells—a discovery recognized by a Nobel Prize—but Duan’s group discovered an amplification step within spinal cord interneurons as crucial for distinguishing cool sensations.

While these findings were made in mice, genetic sequencing indicates all components exist in humans as well. This suggests a similar mechanism likely explains why people can sense relief when entering an air-conditioned space on a hot day.

Looking ahead, Duan’s group plans to investigate pathways involved in acute cold pain: “I think the painful sensations are going to be more complicated,” he said. “When we’re in riskier situations, there could be multiple pathways involved.”

Duan expressed personal motivation behind his work: “In summer, I love walking along Lake Michigan and having a gentle breeze hit my face. I feel very cool, very comfortable,” he said. “But the winter is really terrible for me.”