They found that tooth cells called odontoblasts contain the ion channel transient receptor potential channel 5 (TRPC5), a specialized protein that functions as a cold sensor. Additionally, more TRPC5 is present in teeth with cavities.
Based on prior research, the researchers knew TRPC5 was sensitive to cold, but they didn't know where, specifically, it reacted to temperature. This led them to examine odontoblasts, which reside in the outer zone of tooth pulp, making a natural barrier between hard tissues and soft dental pulp. They found that odontoblasts are necessary for sensing cold stimuli.
"TRPC5 may be an effective target for the treatment of dentin hypersensitivity and inflammatory tooth pain," wrote the group, led by Dr. Laura Bernal from Friedrich Alexander University of Erlangen-Nuremberg in Germany.
Odontoblasts containing the ion channel TRPC5 (green) tightly pack the area between the pulp and the dentin in a mouse's molar. The cells' long-haired extensions fill the thin canals in dentin that extend toward the enamel. Image courtesy of Bernal et al/Science Advances 2021.
Though many patients experience tooth sensitivity, the mechanisms behind cold sensation aren't completely known. One theory has been that tiny canals inside the teeth contain a substance that moves with temperature alterations. Some have suggested that nerves can sense the direction of the movement, signaling whether the tooth is hot or cold.
Bernal and colleagues developed a jaw-nerve preparation that recorded neural activity from intact teeth in mice under anesthesia. When researchers touched the teeth with an ice-cold solution, the drop in temperature prompted neural activity, indicating that the tooth was sensing cold. However, mice without functioning TRPC5 did not have the same reaction.
Extracted human teeth were also analyzed to determine the role tooth decay plays in sensitivity. More TRPC5 resided in human teeth with decay, and TRPC5 sensory nerve expression rose significantly in teeth with pulpitis.
Additionally, TRPC5 may signal protracted pain and operate as an oxidative stress sensor during inflammation. Therefore, TRPC5 may be the target needed to develop treatments for tooth inflammatory pain and sensitivity. This also explains why clove oil, which mostly contains eugenol, has been used as a pain reliever in dentistry for centuries. Clove oil inhibits TRPC5 currents, the authors wrote.
A limitation of the study is that TRPC5 could not be evaluated in response to cold in odontoblasts in live, unanesthetized mice, the authors noted.
Nevertheless, they concluded that the study closed an important gap in the understanding of tooth pain. And now that the knowledge is out there, it opens the door to new treatment options.
"Once you have a molecule to target, there is a possibility of treatment," stated electrophysiologist and senior study author Dr. Katharina Zimmerman in a release.
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