This is the hidden map of cold in the human body

A team led by researcher Félix Viana, co-director of the Sensory Transduction and Nociception laboratory of the Institute of Neurosciences (IN), a joint center of the Higher Council for Scientific Research (CSIC) and the Miguel Hernández University of Elche (UMH), has shown that the body uses different molecular mechanisms to detect cold in the skin and internal organs.

The results of the research, carried out in animal models, imply a “breakthrough” in understanding thermal homeostasis -the body’s ability to maintain a stable internal temperature- and certain diseases of sensitivity to cold, as reported by the center in a statement.

This work, recently published in the journal Acta Physiologica, shows that the perception of cold is not a homogeneous process throughout the organism. on the skin, cold is mainly detected through the TRPM8 ion channelspecialized in recognizing low temperatures and refreshing sensations from the environment. Instead, internal organslike the lungs or the stomach, mainly use another different sensorcalled TRPA1, to perceive temperature decreases, they have indicated.

This difference in molecular mechanisms explains why the sensation of cold on the body surface can be very different to that experienced when breathing cold air or ingesting very cold foods or liquids, since each type of tissue activates and uses different routes to detect thermal changes.

“The skin is equipped with specific sensors that allow us to detect environmental cold and adapt defense behaviors,” explained Félix Viana, principal investigator of the study, and added: “On the other hand, the detection of cold inside the body seems to depend on sensory circuits and molecular receptors distinct, reflecting their deeper physiological role in internal regulation and response to environmental stimuli.

The research team carried out this study using animal models that made it possible to directly analyze the activity of sensory neurons involved in the detection of cold. Specifically, the team compared neurons of the trigeminal nerveresponsible for transmitting information from the skin and the surface of the head, with neurons of the vagus nerve, the main sensory pathway that connects the brain with internal organs such as the lungs and the digestive tract.

To examine how these neurons respond to temperature changesthe researchers used calcium imaging techniques and electrophysiological recordings, which allow neuronal activation to be observed in real time.

These approaches were combined with the use of specific drugs capable of blocking certain molecular sensors, which helped to identify which ion channels are involved in the detection of cold in each type of neuron.

Additionally, the team used genetically modified mice lacking the TRPM8 or TRPA1 sensors, along with gene expression analysis, to confirm the differential role of these channels in cold perception. This multidisciplinary approach allowed us to demonstrate that Cold detection is finely tuned to physiological functions of each tissue and that internal organs use different molecular mechanisms than those of the skin.

“Our findings reveal a more complex and nuanced view of how the sensory systems of different tissues encode thermal information. This opens new lines to study how these signals are integrated and how they can be altered in pathological conditions, such as in certain neuropathies where sensitivity to cold is altered“, highlighted Katharina Gers-Barlag, first author of the article.

This study has been possible thanks to funding from the National Scientific and Technical Research and Innovation Plan of the Government of Spain; from the State Research Agency-Ministry of Science, Innovation and Universities, through the Severo Ochoa Program for Centers of Excellence; and the Generalitat Valenciana.

This work is part of an international project, funded by the Human Frontier Science Program (HFSP) and coordinated by Viana at the Institute of Neurosciences, whose objective is to study the molecular bases of cold perception in different species adapted to extreme thermal environments.