November 30, 2023

There’s nothing like the strange, bone-shaking reaction of a damaged tooth exposed to something cold: a bite of ice or a cold drink and suddenly that sharp, searing sensation, like a needle piercing a nerve.

Researchers have known for years that this phenomenon is due to damage to the outer protective layer of the tooth. But how the message gets from the outside of your tooth to the nerves inside has been difficult to detect. On Friday, biologists reported in Science Advances magazine that they identified an unexpected player for that painful sensation: a protein embedded in the surface of cells inside teeth. The discovery offers insight into the connection between the outside world and the inside of a tooth and could one day guide the development of treatments for toothache.

More than a decade ago, Dr. Katharina Zimmerman, now a professor at Friedrich-Alexander-Universität in Germany, discovered that cells that produce a protein called TRPC5 are sensitive to cold. When it got cold, TRPC5 opened and formed a channel for ions to flow across the cell membrane.

Ion channels like TRPC5 are distributed throughout our bodies, said Dr. Zimmerman, and they are behind some surprisingly familiar sensations. For example, if your eyes feel cold and dry in cold air, an ion channel in the cornea is activated. She wondered what other parts of the body might be using a cold receptor like TRPC5. And it occurred to her that “the most sensitive tissue in the human body can be teeth” when it comes to cold sensations.

In the protective covering of their enamel, teeth are made of a hard substance called dentin that is threaded through tiny tunnels. The heart of dentin is the soft pulp of the tooth, in which nerve cells and cells, so-called odontoblasts, that make dentin, are intertwined.

The prevailing theory of how teeth perceive cold was that changes in temperature put pressure on the fluid in dentin tunnels and somehow provoke a response in those hidden nerves. But there was little detail on how exactly that could happen and what could bridge the gap between them.

Dr. Zimmerman and her colleagues examined whether mice that lacked the TRPC5 channel still experienced toothache, as did normal mice. They were intrigued to find that when these mice damaged their teeth, they didn’t act like something was wrong. In fact, they looked something like they’d been given an anti-inflammatory pain reliever, said Dr. Zimmerman.

Your co-author Dr. Jochen Lennerz, a pathologist at Massachusetts General Hospital, examined human teeth for signs of the ion channel and found them in their nerves and other cells. This suggested that the channel might play a role in a person’s perception of cold.

Over many years, the researchers developed a method to precisely measure the nerve signals emerging from a mouse’s damaged molar. They tested their ideas with molecules that could block the activity of various channels, including TRPC5.

The picture they slowly compiled is that TRPC5 is active in the odontoblasts. That was a bit of a surprise, as these support cells are best known for making and maintaining dentin without aiding the perception. Inside the odontoblasts, said Dr. Lennerz, TRPC5 opens when the cold signal comes through the dentinal tunnel, and this causes a message to be sent to the nerves.

One substance that prevents TRPC5 from opening is eugenol, the main ingredient in clove oil, a traditional treatment for toothache. Although the US Food and Drug Administration does not clearly assess the effectiveness of eugenol, it may be due to the effects of TRPC5 in relieving pain in some people.

Perhaps knowing that this canal is at the heart of cold-induced pain will lead to better treatments for toothache in the future – better ways to keep this message from becoming overwhelming.