Scientists have known the causes of cold-related tooth pain for a while—cavities, receding gums and the side effects of chemotherapy are often the culprits.
But until recently, the process by which teeth sense cold and transmit pain signals to the brain has been a mystery.
A team of researchers from Massachusetts General Hospital and Friedrich-Alexander University (FAU) in Germany have discovered a key player in the process—a type of cells called odontoblasts.
Jochen Lennerz, MD, PhD
Odontoblasts were previously known as the starter cells that form dentin—the shell underneath the tooth’s enamel that encases the soft inner tooth called the pulp.
In a recent study in Science Advances, the researchers demonstrated that odontoblasts are also responsible for sensing cold and transmitting that signal to the brain.
The team’s discovery also shed light on how clove oil, a common remedy for tooth pain, works on a mechanistic level. These insights could inform the development of new therapeutics to relieve tooth pain.
Getting to the Root of Tooth Pain
Previous research by co-senior author Katharina Zimmermann, MD, PhD, of Friedrich-Alexander University, identified a protein called TRPC5, which is expressed in the nerves in many parts of the body, as a target of interest for tooth pain.
To learn more about TRPC5, the team drilled holes in the molars of two sets of anesthetized mice. One set of mice were genetically engineered to remove the gene responsible for producing TRPC5, while the control group still had the gene intact.
Following the drilling, the mice without the gene for TRPC5 did not manifest the same pain-soothing behavior (drinking up to 300% more sugar water) than the mice in the control group, suggesting they were not experiencing the same discomfort.
Further research revealed that when exposed to cold temperatures, the TRPC5 protein opens channels enabling other molecules, such as calcium, to interact with the cells and enabling the transmission of nerve signals from the pulp to the brain.
“Most cells and tissues slow their metabolism in the presence of cold, which is why donor organs are put on ice,” says co-senior author Jochen Lennerz, MD, PhD, director of the Center for Integrated Diagnostics at Massachusetts General Hospital and an associate professor of pathology at Harvard Medical School. “But TRPC5 makes cells more active in cold, and the odontoblasts’ ability to sense cold via TRPC5 makes this discovery so exciting.”
To confirm the presence of TRPC5 in human teeth, Lennerz and his team developed a technologically advanced processes to soften the teeth before slicing them into thin layers, where the team was able to identify TRPC5 channels in odontoblasts.
A New Treatment Target
For centuries, oil of cloves has been used to relieve tooth pain. The active ingredient in clove oil is eugenol, which blocks TRPC5. There are already toothpastes on the market that contain eugenol, which explains how they help to relieve cold sensitivity.
But the team’s findings could also help in developing more advanced eugenol-based therapies to help cancer patients with extreme cold sensitivity due to chemotherapy treatments.
The team is currently looking for partners to develop the commercial potential of their findings. For example, new modalities of applying these TRPC5 inhibitors may include chewing gum against cold-sensitive teeth.
“This research contributes a new function to odontocytes, which is exciting from a basic-science standpoint,” says Lennerz. “But we now also know how to interfere with this cold-sensing function to inhibit dental pain.”
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