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Researchers report in Science Advances that they have discovered a new function for odontoblasts, the cells that make up dentin, the shell under tooth enamel that envelops the soft dental pulp containing nerves and blood vessels. “We found that odontoblasts, which support the shape of the tooth, are also responsible for detecting cold,” says pathologist Jochen Lennerz, MD, PhD, one of the lead authors of the article and medical director of the Massachusetts General Hospital Center for Integrated Diagnostics. (MGH). “This research brings a new function to this cell, which is exciting from a fundamental science point of view. But we now also know how to interfere with this cold sensing function to inhibit dental pain.”
Teeth injured by exposure to cold can occur for several reasons. Many people have experienced severe pain from the cold when they have a hole in a tooth from an untreated cavity, for example. But teeth can also become very sensitive to cold due to erosion of the gums due to aging. Some cancer patients treated with platinum-based chemotherapy drugs have extreme sensitivity to cold all over their body. “A breeze on the face is considered extreme pain in the teeth, which may even cause some patients to stop treatment,” says Lennerz.
Tooth pain has been notoriously difficult to study. The hardness of a tooth makes it difficult to study, and the induction of dental pain in humans requires opening the tooth. The team of researchers therefore carried out experiments on mice whose molars were drilled under anesthesia. Mice with dental injuries show pain with their behavior; they drink up to 300% more sugar water than their litter mates without dental injuries, for example. In previous research, the team of researchers discovered TRCP5, a protein encoded by the TRCP5 gene that is expressed in nerves in many parts of the body. Their earlier discovery allowed researchers to focus on TRCP5 as a mediator of cold pain.
By studying genetically engineered mice that lacked the TRCP5 gene, the researchers found that mice with injured teeth did not exhibit increased drinking behavior and behaved like mice without dental injuries.
“We now have definitive proof that the TRCP5 temperature sensor transmits cold through odontoblast and sets the nerves on fire, creating pain and hypersensitivity to cold,” says Lennerz. “This sensitivity to cold may be the body’s way of protecting a damaged tooth from further injury.”
Specifically, in response to cold, the TRCP5 protein opens channels in the membrane of odontoblasts, allowing other molecules, such as calcium, to enter and interact with the cell. If the tooth pulp is inflamed from a deep cavity, for example, TRCP5 is overabundant, causing an increase in electrical signaling via nerves emerging from the tooth root and running to the brain, where pain is perceived. As the gums recede with aging, teeth can become hypersensitive because odontoblasts sense cold in a newly exposed area of the tooth. “Most cells and tissues slow down their metabolism in the presence of cold, which is why donor organs are put on ice,” says Lennerz. “But TRPC5 makes cells more active in the cold, and the ability of odontoblasts to sense cold via TRPC5 makes this discovery so exciting.”
Lennerz confirmed the presence of the TRPCS protein in extracted human teeth, which was a technical feat. “Our teeth are not meant to be cut in ultra-thin layers so that they can be studied under a microscope,” says Lennerz, who first had to decalcify the teeth and put them in epoxy resin before slicing and dyeing them. ‘identify TRPC5 channels in odontoblasts.
The research team also identified a pharmacological target to minimize the sensitivity of teeth to cold. For centuries, clove oil has been used as a remedy for dental pain. The active agent in clove oil is eugenol, which blocks TRCP5. Toothpastes containing eugenol are already on the market, but the results of this study could lead to more powerful applications for treating teeth that are hypersensitive to cold. And there may be new applications for eugenol, such as systemic treatment of patients for extreme cold sensitivity due to chemotherapy. “I am delighted to see how other researchers will apply our results,” says Lennerz. (ANI)
Teeth injured by exposure to cold can occur for several reasons. Many people have experienced severe pain from the cold when they have a hole in a tooth from an untreated cavity, for example. But teeth can also become very sensitive to cold due to erosion of the gums due to aging. Some cancer patients treated with platinum-based chemotherapy drugs have extreme sensitivity to cold all over their body. “A breeze on the face is considered extreme pain in the teeth, which may even cause some patients to stop treatment,” says Lennerz.
Tooth pain has been notoriously difficult to study. The hardness of a tooth makes it difficult to study, and the induction of dental pain in humans requires opening the tooth. The team of researchers therefore carried out experiments on mice whose molars were drilled under anesthesia. Mice with dental injuries show pain with their behavior; they drink up to 300% more sugar water than their litter mates without dental injuries, for example. In previous research, the team of researchers discovered TRCP5, a protein encoded by the TRCP5 gene that is expressed in nerves in many parts of the body. Their earlier discovery allowed researchers to focus on TRCP5 as a mediator of cold pain.
By studying genetically engineered mice that lacked the TRCP5 gene, the researchers found that mice with injured teeth did not exhibit increased drinking behavior and behaved like mice without dental injuries.
“We now have definitive proof that the TRCP5 temperature sensor transmits cold through odontoblast and sets the nerves on fire, creating pain and hypersensitivity to cold,” says Lennerz. “This sensitivity to cold may be the body’s way of protecting a damaged tooth from further injury.”
Specifically, in response to cold, the TRCP5 protein opens channels in the membrane of odontoblasts, allowing other molecules, such as calcium, to enter and interact with the cell. If the tooth pulp is inflamed from a deep cavity, for example, TRCP5 is overabundant, causing an increase in electrical signaling via nerves emerging from the tooth root and running to the brain, where pain is perceived. As the gums recede with aging, teeth can become hypersensitive because odontoblasts sense cold in a newly exposed area of the tooth. “Most cells and tissues slow down their metabolism in the presence of cold, which is why donor organs are put on ice,” says Lennerz. “But TRPC5 makes cells more active in the cold, and the ability of odontoblasts to sense cold via TRPC5 makes this discovery so exciting.”
Lennerz confirmed the presence of the TRPCS protein in extracted human teeth, which was a technical feat. “Our teeth are not meant to be cut in ultra-thin layers so that they can be studied under a microscope,” says Lennerz, who first had to decalcify the teeth and put them in epoxy resin before slicing and dyeing them. ‘identify TRPC5 channels in odontoblasts.
The research team also identified a pharmacological target to minimize the sensitivity of teeth to cold. For centuries, clove oil has been used as a remedy for dental pain. The active agent in clove oil is eugenol, which blocks TRCP5. Toothpastes containing eugenol are already on the market, but the results of this study could lead to more powerful applications for treating teeth that are hypersensitive to cold. And there may be new applications for eugenol, such as systemic treatment of patients for extreme cold sensitivity due to chemotherapy. “I am delighted to see how other researchers will apply our results,” says Lennerz. (ANI)
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