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Biting something cold with a damaged or sensitive tooth can trigger a particularly excruciating type of pain, but scientists have never fully understood how this pain signal is transmitted. Now, they’ve found a prime suspect: a protein called TRPC5.
The protein is found in cells called odontoblasts inside the teeth, which form the dentin shell just below the enamel. Odontoblasts support the shape of the tooth; as researchers have now discovered, these cells also act as cold catchers.
They can do this because TRPC5 is an ion channel – a gateway that helps signal chemicals, such as calcium, across cell membranes under certain conditions; in this case, they react to cold.
New treatments could be developed based on these findings to help relieve pain or hypersensitivity in teeth – perhaps given through chewing gum or strips applied directly to dentin.
“This research brings a new function to this cell, which is exciting from a basic science perspective,” says pathologist Jochen Lennerz of Massachusetts General Hospital. “But we now also know how to interfere with this cold sensing feature to inhibit dental pain.”
Having previously identified TRPC5 as a potential temperature sensor, in experiments with mice, the team found that those lacking the gene encoding TRPC5 did not respond to exposure of teeth to cold in the usual way. . The use of chemicals to block protein ion channels had the same effect.
TRPC5 (in green) inside a mouse tooth. (L. Bernal et al./Science Advances 2021)
Thorough analysis of the extracted human teeth – they were decalcified, then placed in epoxy resin, then carefully sliced - revealed the same TRPC5 channels in odontoblast cells, suggesting that the same detection also occurs in human teeth.
The TRPC5 protein is found elsewhere in the body, and has already been shown to detect cold and trigger certain biological actions. Now we know it works inside odontoblasts in teeth as well, and it could mean some relief for the roughly 2.4 billion people living with untreated dental caries.
In addition to all this, this new study also helps explain why clove oil has been used for centuries as a treatment for dental pain: its active agent is eugenol, which is found to block TRPC5. No wonder people traditionally use the oil to reduce sensitivity.
“Once you have a molecule to target, there is a possibility of treatment,” explains electrophysiologist Katharina Zimmermann, of the Friedrich-Alexander Erlangen-Nürnberg University in Germany.
Teeth can become sensitive to cold due to cavities, due to erosion of the gums due to aging and for many other reasons – this is one of the side effects of some type of chemotherapy treatment. , which may even deter patients from taking the drugs. .
The researchers suggest that sensitivity to cold could be a warning signal to the body to help prevent further damage to the tooth – odontoblast cells become more active in the cold, a drop in temperature which usually means the tooth is more exposed.
Human teeth are very difficult to study and the research as a whole has spanned over a decade, but now the new role of TRPC5 and odontoblast cells is something that future research can explore.
“Our teeth are not meant to be cut into ultra-thin layers so that they can be studied under a microscope,” says Lennerz. “I am delighted to see how other researchers will apply our results.”
The research was published in Scientific progress.
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