There is nothing like the peculiar reaction of breaking the bones of a damaged tooth exposed to something cold: a bite of ice cream or a cold drink and, suddenly, that sharp, scorching sensation, like a needle piercing a nerve.
Researchers have known for years that this phenomenon results from damage to the tooth’s protective outer layer. But it is difficult to discover how the message goes from outside the tooth to the nerves within it. On Friday, biologists reported in Science Advances that they identified an unexpected player in this painful sensation: a protein embedded in the surface of cells inside the teeth. The discovery provides a glimpse of the connection between the outside world and the inside of a tooth and may one day help guide the development of treatments for toothache.
More than a decade ago, Dr. Katharina Zimmerman, now a professor at Friedrich-Alexander University in Germany, discovered that cells that produce a protein called TRPC5 were sensitive to cold. When things cooled down, TRPC5 opened up to form a channel, allowing ions to flow through the cell’s membrane.
Ion channels like TRPC5 are scattered throughout our bodies, said Zimmerman, and are behind some surprisingly familiar sensations. For example, if your eyes start to get cold and dry in the cold air, it is the result of an ion channel being activated in the cornea. She wondered what other parts of the body could use a cold receiver like TRPC5. And it occurred to her that “the most sensitive tissue in the human body may be the teeth” when it comes to sensations of cold.
Inside the protective shell of your enamel, your teeth are made of a hard substance called dentin, which is interspersed by tiny tunnels. At the heart of dentin is the soft pulp of the tooth, where nerve cells and cells called odontoblasts, which make dentin, are intertwined.
The prevailing theory about how teeth feel cold was that changes in temperature pressured the fluid in the dentin tunnels, somehow eliciting a response in these hidden nerves. But there was little detail about exactly how this could be happening and what could be filling the gap between them.
Dr. Zimmerman and his colleagues looked to see if mice designed not to have the TRPC5 channel still felt toothache like normal mice. They were intrigued to discover that these mice, when they damaged their teeth, did not behave as if something was wrong. They looked, in fact, as if they had received an anti-inflammatory painkiller, said Zimmerman.
Its co-author, Dr. Jochen Lennerz, a pathologist at Massachusetts General Hospital, scanned human teeth for ion channel signals and found it in his nerves and other cells. This suggested that the channel may have a role in a person’s perception of cold.
Over many years, researchers have devised a way to accurately measure nerve signals coming out of a mouse’s damaged molar. They tested their ideas with molecules that could block the activity of several channels, including TRPC5.
The image that they slowly put together is that TRPC5 is active in odontoblasts. This was a little surprising, as these support cells are best known for making and maintaining dentin, not aiding perception. Within the odontoblasts, Lennerz said, the TRPC5 opens when the cold signal descends through the dentin tunnels, and this results in a message being sent to the nerves.
Incidentally, a substance that prevents TRPC5 from opening is eugenol, the main ingredient in clove oil, a traditional treatment for toothache. Although the United States Food and Drug Administration is ambiguous about the effectiveness of eugenol, if it lessens pain for some people, it may be because of its effect on TRPC5.
Perhaps the knowledge that this channel is at the heart of cold-induced pain will lead to better treatments for dental pain in the future – better ways to prevent this message from becoming overwhelming.