Your body feels cold in two different ways

The findings were published in the scientific journal Acta Physiologica and show that cold perception varies depending on where it occurs in the body. In the skin, low temperatures are mainly detected by an ion channel called TRPM8, which is specialized for sensing cool environmental conditions. Inside the body, however, organs such as the lungs and stomach depend largely on a different molecular sensor known as TRPA1 to register temperature changes.

Why Cold Feels Different on Skin and Inside the Body

This division helps explain a familiar experience: cold on the skin feels very different from the sensation of breathing icy air or swallowing a cold drink. Each tissue type activates its own biological pathways to detect temperature shifts. As Félix Viana explains, "The skin is equipped with specific sensors that allow us to detect environmental cold and adapt defensive behaviors." He adds: "In contrast, cold detection inside the body appears to depend on different sensory circuits and molecular receptors, reflecting its deeper physiological role in internal regulation and responses to environmental stimuli."

Studying Cold-Sensing Nerves

To uncover these differences, the researchers used animal models that made it possible to directly study the sensory neurons responsible for detecting cold. They focused on two major nerve pathways. One was the trigeminal nerve, which carries sensory information from the skin and surface of the head. The other was the vagus nerve, a key communication route between the brain and internal organs such as the lungs and digestive system.

The team examined how neurons from these nerves responded to temperature changes using calcium imaging and electrophysiological recordings. These techniques allowed scientists to observe nerve activity in real time. They also applied drugs that selectively block certain molecular sensors, making it possible to pinpoint which ion channels were active in each type of neuron.

Genetic Evidence Confirms Distinct Roles

The researchers further strengthened their findings by studying genetically modified mice that lacked either the TRPM8 or TRPA1 sensors. By combining these experiments with gene expression analyses, they confirmed that each sensor plays a distinct role in cold perception depending on the tissue involved. The results show that temperature detection is closely matched to the specific physiological role of each part of the body, with internal organs using molecular mechanisms that differ from those found in the skin.

Katharina Gers-Barlag, first author of the study, emphasizes the broader significance of the work. "Our findings reveal a more complex and nuanced view of how sensory systems in different tissues encode thermal information. This opens new avenues to study how these signals are integrated and how they may be altered in pathological conditions, such as certain neuropathies in which cold sensitivity is disrupted."

Funding and International Collaboration

The research was supported by multiple funding sources, including the Spanish National Plan for Scientific and Technical Research and Innovation; the Spanish State Research Agency-Ministry of Science, Innovation and Universities, through the Severo Ochoa Programme for Centres of Excellence; and the Valencian Regional Government (Generalitat Valenciana). The study is also part of an international project funded by the Human Frontier Science Program (HFSP) and coordinated by Viana at the Institute for Neurosciences, which aims to understand the molecular foundations of cold perception in species adapted to extreme thermal environments.