A team of researchers led by Félix Viana, co-director at the Institute for Neurosciences (IN), has identified that the body uses separate molecular mechanisms to sense cold in the skin and internal organs. The IN is a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche (UMH). The findings were published in Acta Physiologica.
According to the study, cold detection across the body is not uniform. The skin senses environmental cold primarily through an ion channel called TRPM8. Internal organs such as the lungs and stomach rely on a different sensor, TRPA1, to detect decreases in temperature.
This distinction helps explain why feeling cold on the skin differs from sensations when inhaling cold air or consuming very cold food or beverages. "The skin is equipped with specific sensors that allow us to detect environmental cold and adapt defensive behaviours," said Félix Viana, principal investigator of the study. He added: "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 research used animal models to directly analyze sensory neurons involved in detecting cold. Scientists compared neurons from the trigeminal nerve—which conveys information from the skin and head surface—to those from the vagus nerve, which links the brain with internal organs like the lungs and digestive tract.
To observe neuronal responses to temperature changes, techniques such as calcium imaging and electrophysiological recordings were used for real-time monitoring. Researchers also applied pharmacological agents that block specific molecular sensors, helping identify which ion channels are responsible for detecting cold in each neuron type.
Genetically modified mice lacking either TRPM8 or TRPA1 were used along with gene expression analyses to confirm these channels' distinct roles in perceiving cold. This approach showed that each tissue's physiological function aligns with how it detects thermal changes.
Funding for this research came from several sources including Spain’s National Plan for Scientific and Technical Research and Innovation; support from Spain’s State Research Agency–Ministry of Science, Innovation and Universities via its Severo Ochoa Programme; as well as backing from the Valencian Regional Government (Generalitat Valenciana). The project is part of an international effort supported by the Human Frontier Science Program (HFSP) under Viana’s coordination at IN.
