Scientists unveil a comprehensive skin-to-brain neural pathway for temperature detection, a breakthrough that may stimulate medical advancements, including novel therapies for temperature-related discomfort.
Researchers from the University of Michigan have clarified a complete sensory pathway demonstrating how the skin relays its temperature information to the brain.
This revelation, thought to be the first of its type, shows that cool temperatures possess their unique pathway, suggesting that evolution has developed distinct circuits for extreme heat and cold. This forms a sophisticated mechanism to ensure accurate thermal perception and suitable behavioral reactions to changes in the environment, explained Bo Duan, lead author of the latest study.
“The skin is the largest organ in the body. It aids us in perceiving our environment and distinguishing various stimuli,” remarked Duan, U-M associate professor of molecular, cellular, and developmental biology. “There remain numerous fascinating inquiries concerning how this occurs, but we have now established a pathway for sensing cool temperatures. This represents the first clearly identified neural circuit for temperature sensation running from the skin to the brain.”
This research enhances our understanding of fundamental biology and brings us closer to explaining how we evolved to thrive within safe temperature ranges and steer clear of extreme conditions, Duan noted. Additionally, it carries medical implications that could enhance individuals’ quality of life in the future.
For instance, over 70% of individuals who have undergone chemotherapy suffer from pain induced by cooler temperatures, Duan mentioned. The new research revealed that the neural circuit responsible for detecting harmless cool sensations does not mediate this type of cold-induced pain. Yet, by examining the proper functioning of the cool-sensing circuit under normal circumstances, researchers are now better positioned to identify discrepancies that arise during disease or injury. It may also aid in the development of targeted therapies that restore healthy sensation without compromising regular temperature perception.
This study received funding from the National Institutes of Health and was conducted in collaboration with Shawn Xu and his research group at the U-M Life Sciences Institute.
Discovery of a cool amplifier
In their research, published in the journal Nature Communications, Duan and his team utilized advanced imaging methods and electrophysiology to investigate how mice conveyed cool temperature sensations from their skin to their brain.
This method had previously been employed by the team for other sensory modalities. Led by postdoctoral research fellow Hankyu Lee along with doctoral students Chia Chun Hor and Lorraine Horwitz, the team pivoted their focus to temperature in this investigation.
“These tools have enabled us to identify neural pathways for chemical itch and mechanical itch in the past,” stated Duan. “Collaboratively, the team uncovered this fascinating and dedicated pathway for cool sensation.”
The cool signal originates in the skin, home to molecular sensors capable of detecting a specific temperature range between approximately 15 and 25 degrees Celsius—comparable to 59 and 77 degrees Fahrenheit. Upon activation of these sensors, they stimulate primary sensory neurons that relay the cool signal to the spinal cord. Here, the researchers found that the signal is amplified by specialized interneurons, which subsequently activate projection neurons that connect to the brain.
While researchers had previously recognized the skin’s molecular temperature sensors—contributing to a 2021 Nobel Prize in Physiology or Medicine awarded to scientists in California—the spinal cord’s amplifier was an unrecognized essential element. The team discovered that without this amplifier, the cool signal is overwhelmed by noise.
Although the study was conducted in mice, each component of the circuit has been found in humans via genetic sequencing, Duan noted. Therefore, it is likely that we share the same pathway responsible for the refreshing experience of entering an air-conditioned space on a hot summer day.
Moving forward, the team aims to identify the pathways associated with acute cold pain.
“I suspect that painful sensations will prove to be more complex,” Duan remarked. “In more challenging situations, multiple pathways may be implicated.”
His team also seeks to investigate how the brain interprets these various skin signals and how we have evolved not only to identify them but also to associate emotions with them for self-protection. Indeed, it is this curiosity surrounding such questions that initially inspired Duan’s research, a drive that he is continually reminded of during his time in Michigan.
“In summer, I thoroughly enjoy walking along Lake Michigan and feeling a gentle breeze on my face. It feels so refreshing and comfortable,” Duan shared. “However, the winter is genuinely harsh for me.”