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A new discovery of how mammals feel cold can lead to new pain remedies



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UCL researchers have shown for the first time that mammals detect different cold intensities using different sensory neuronal systems, which could lead to the development of new drugs for the treatment of cold pain.

Study in mice, published in Proceedings of the National Academy of Sciences, they have been asked to understand more about two known sensory neuronal (nerve) populations that mammals use in the cold sense. Namely, neuronal populations expressing the ion channel Transient receptor potential of melastatin 8 (Trpm8), or sodium channel NaV1.8.

The researchers used in vivo GCaMP3 imaging to identify populations of sensory neurons in live mice. The study showed that Trpm8 neurons detect changes in body temperature to zero degrees (acute cold), and that NaV1.8 expressing neurons detect prolonged extreme (harmful) coldness below zero.

Author collaborator dr. Edvard Emeri (Institute of Biomedical Research, UCL Wolfson for Biomedical Research) said: "Trpm8 and NaV1.8 are not generally expressed in the same neuron set, which historically represented a significant challenge in understanding how both of these molecular targets can be independently responsible for cold readings.

"We show that the vast majority of acutely cold-sensitive neurons do not express Nav1.8, but are enriched with Trpm8, as well as a unique repertoire of other genes.

"In contrast, we see a key role for NaV1.8 in detecting extended extreme cold.

"These results greatly improve our understanding of how these different peripheral sensory neurons feel acute and long-lasting harmful cold, and show that multiple cell and molecular mechanisms contribute to cold pain in mammals."

Observing that different neuronal populations are responsible for detecting different cooling intensities can facilitate the development of more effective therapies for cold-related pain.

The author of co-author Professor John Wood (Institute of Biomedical Research, UCL Wolfson) said: "Cold sensation in mammals is a necessary means of survival with almost all parts of the world that have a cold season."

"However, some people with nerve damage often feel cold, when in fact the ambient temperature does not cause a cold sensation.

"Our new finding can now allow researchers to master possible key causes and develop drugs to block cold pain, depending on which nerves are damaged."

Study limitations

One of the key findings of our research is that potassium channels can play a key role in modulating our ability to detect the coolness of the environment. It is important that there are many different types of potassium channels expressed in sensory neurons, where they play a key role in regulating neuronal excitability. This means that the specificity of the drug, as well as the overcoming of potential compensation with other potassium channels, will be vital for the development of effective therapeutics that do not affect the normal sensory function.


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More information:
A. P. Luiz et al., Cold sensors with NaV1.8-positive and NaV1.8-negative sensory neurons, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073 / pnas.1814545116

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University College London

Citation:
A new discovery of how mammals feel cold can lead to new pain relief drugs (2019, April 24)
taken on April 24, 2019
from https: //medicalkpress.com/nevs/2019-04-discoveri-mammals-cold-pain-relief.html

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