For people with tooth decay, drinking a cold beverage can be agony. Now an international team of scientists have figured out how teeth sense the cold and pinpointed the molecular and cellular players involved—and published their findings in published in Science Advances.
Teeth decay when films of bacteria and acid eat away at the enamel. As enamel erodes, pits called cavities form. Roughly a third of the world’s population have untreated cavities in permanent teeth, which can cause intense pain, including extreme cold sensitivity.
No-one really knew how teeth sensed the cold, though scientists had proposed one main theory. Tiny canals inside the teeth contain fluid that moves when the temperature changes. Somehow, nerves can sense the direction of this movement, which signals whether a tooth is hot or cold, some researchers have suggested.
The research team led by electrophysiologist Katharina Zimmermann, from Friedrich-Alexander University Erlangen-Nürnberg in Germany, didn’t set out to study teeth. Their work focused primarily on ion channels, pores in cells’ membranes that act like molecular gates. After detecting a signal—a chemical message or temperature change, for example—the channels either clamp shut or open wide and let ions flood into the cell. This creates an electrical pulse that zips from cell to cell. It’s a rapid way to send information, and crucial in the brain, heart, and other tissues.
About 15 years ago, the team discovered that an ion channel called TRPC5 was highly sensitive to the cold. But they didn’t know where in the body TRPC5’s cold-sensing ability came into play. It wasn’t the skin, they found.
But TRPC5, it was discovered, does reside in teeth—and more so in teeth with cavities.
A novel experimental set-up in mice convinced the researchers that TRPC5 indeed functions as a cold sensor. Instead of cracking a tooth open and solely examining its cells in a dish, Zimmermann’s team looked at the whole system: jawbone, teeth, and tooth nerves. The team recorded neural activity as an ice-cold solution touched the tooth. In normal mice, this frigid dip sparked nerve activity, indicating the tooth was sensing the cold. Not so in mice lacking TRPC5 or in teeth treated with a chemical that blocked the ion channel. That was a key clue that the ion channel could detect cold. One other ion channel the team studied, TRPA1, also seemed to play a role.
The team traced TRPC5’s location to a specific cell type, the odontoblast, that resides between the pulp and the dentin. When someone with a dentin-exposed tooth bites down on a popsicle, for example, those TRPC5-packed cells pick up on the cold sensation and an ‘ouch!’ signal speeds to the brain.