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 research conducted on animal models represent an “advancement” in understanding thermal homeostasis – the body’s ability to maintain a stable internal temperature – and certain diseases due to sensitivity to cold, the center reported 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. In the skin, cold is detected primarily via the TRPM8 ion channel, which is specialized in detecting low temperatures and refreshing sensations from the environment. On the other hand, internal organs such as the lungs or stomach mainly use another sensor called TRPA1 to sense temperature drops, as they stated.
This difference in molecular mechanisms explains why the sensation of cold on the surface of the body can be very different from that experienced when breathing in cold air or consuming very cold foods or liquids, because each type of tissue activates and uses different pathways to detect thermal changes.
“The skin is equipped with specific sensors that allow us to detect environmental cold and adapt defensive behaviors,” explained Félix Viana, principal investigator of the study, adding: “In contrast, the detection of cold in the body appears to depend on different sensory circuits and molecular receptors, reflecting its deeper physiological role in internal regulation and response to environmental stimuli.”
The research team conducted this study using animal models, which made it possible to directly analyze the activity of sensory neurons involved in detecting cold.
Specifically, the team compared neurons in the trigeminal nerve, which is responsible for transmitting information from the skin and surface of the head, with neurons in the vagus nerve, the main sensory pathway that connects the brain to internal organs such as the lungs and digestive tract.
To study how these neurons respond to temperature changes, 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 that can block specific molecular sensors, which helped identify which ion channels are involved in detecting cold in each type of neuron.
In addition, the team used genetically modified mice lacking the TRPM8 or TRPA1 sensors and gene expression analysis to confirm the distinct roles of these channels in cold perception. With this multidisciplinary approach, we were able to show that cold detection is precisely tailored to the physiological functions of each tissue and that internal organs use different molecular mechanisms than the skin.
“Our results reveal a more complex and nuanced view of how the sensory systems of different tissues encode thermal information. This opens up new possibilities for studying how these signals are integrated and how they can be altered in pathological conditions, for example in certain neuropathies in which cold sensitivity is altered,” said Katharina Gers-Barlag, first author of the article.
This study was possible thanks to funding from the National Plan for Scientific and Technical Research and Innovation of the Spanish Government; from the State Research Agency – Ministry of Science, Innovation and Universities, through the Severo Ochoa Centers of Excellence Program; 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 Neuroscience. The aim of the project is to investigate the molecular basis of cold perception in different species adapted to extreme thermal environments.
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