A research team led by Félix Viana, co-director of the Sensory Transduction and Nociception laboratory at the Institute for Neurosciences (IN), a joint research centre of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche (UMH), has demonstrated that the body uses different molecular mechanisms to detect cold in the skin and in internal organs. These findings represent a significant advance in understanding thermal homeostasis and certain pathologies associated with cold sensitivity.
The study, recently published in the journal Acta Physiologica , shows that cold perception is not a homogeneous process throughout the organism. In the skin, cold is mainly detected through the ion channel TRPM8, which is specialised in sensing low temperatures and cooling sensations from the environment. In contrast, internal organs such as the lungs or the stomach primarily rely on a different sensor, known as TRPA1, to perceive temperature decreases.
This difference in molecular mechanisms explains why the sensation of cold on the body surface can be very different from that experienced when breathing cold air or ingesting very cold food or drinks, as each type of tissue activates and uses distinct pathways to detect thermal changes. "The skin is equipped with specific sensors that allow us to detect environmental cold and adapt defensive behaviours", explains Félix Viana, principal investigator of the study. 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".
The study was carried out using animal models that allowed direct analysis of the activity of sensory neurons involved in cold detection. Specifically, the team compared neurons from the trigeminal nerve, which transmits information from the skin and the surface of the head, with neurons from the vagus nerve, the main sensory pathway connecting the brain with internal organs such as the lungs and the digestive tract.
To examine how these neurons respond to temperature changes, the researchers used calcium imaging techniques and electrophysiological recordings, allowing real-time monitoring of neuronal activation. These approaches were combined with the use of specific pharmacological agents capable of blocking particular molecular sensors, helping to identify which ion channels are involved in cold detection in each type of neuron.
In addition, the team used genetically modified mice lacking the TRPM8 or TRPA1 sensors, together with gene expression analyses, to confirm the differential role of these channels in cold perception. This multidisciplinary approach demonstrated that cold detection is finely tuned to the physiological functions of each tissue and that internal organs employ molecular mechanisms distinct from those used by the skin.
"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," highlights Katharina Gers-Barlag, first author of the article.
This study was made possible thanks to funding from 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 work is part of an international project funded by the Human Frontier Science Program (HFSP) and coordinated by Viana at the Institute for Neurosciences , aimed at studying the molecular bases of cold perception in different species adapted to extreme thermal environments.
