The mysterious molecular culprit behind Cold Tooth Pain

The mysterious molecular culprit behind Cold Tooth Pain

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There is no such thing as the weird, heartbreaking reaction of a damaged tooth exposed to something cold: a bite of ice or a cold drink, and suddenly, that sharp, burning sensation, like a needle piercing a nerve.

Researchers have known for years that this phenomenon results from damage to the protective outer layer of the tooth. But how the message gets from the outside of your tooth to the nerves inside has been hard to find. On Friday, biologists reported in the journal Science Advances to have identified an unexpected player in this painful sensation: a protein embedded in the surface of cells inside the teeth. The discovery provides insight into the connection between the outside world and the inside of a tooth, and may one day help guide the development of treatments for dental pain.

Over ten years ago, Dr. Katharina Zimmerman, now a professor at Friedrich-Alexander University in Germany but then doing postdoctoral research in David Clapham’s lab at Harvard Medical School, discovered that cells producing a protein called TRPC5 were sensitive to cold. When things cooled, TRPC5 opened up to form a channel, allowing ions to flow through the cell membrane.

Ion channels like TRPC5 are sprinkled all over our bodies, Dr. Zimmerman said, and they are the source of surprisingly familiar sensations. For example, if your eyes start to feel cold and dry in cold air, this is the result of the activation of an ion channel in the cornea. She wonders what other parts of the body might be using a cold receptor like TRPC5. And it occurred to him that “the most sensitive tissues in the human body can be the teeth” when it comes to cold sensations.

Inside the protective shell of their enamel, teeth are made of a hard substance called dentin, threaded through 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 dominant theory for how teeth feel cold was that changes in temperature put pressure on the fluid in the dentin tunnels, causing a response in these hidden nerves to some extent. But there were few details on how exactly this could happen and what might bridge the gap between them.

Dr Zimmerman and his colleagues investigated whether mice designed to lack the TRPC5 channel still experienced toothache like normal mice. They were intrigued to find that these mice, when they had damaged teeth, didn’t behave like something was wrong. They actually looked pretty much the same as if they’d been given an anti-inflammatory pain reliever, Dr Zimmerman said.

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

For many years, researchers have built a way to accurately measure the nerve signals coming out of the damaged molar of a mouse. They tested their ideas with molecules that could block the activity of various channels, including TRPC5.

The image that they have slowly assembled is that TRPC5 is active in odontoblasts. This was a bit of a surprise, as these supporting cells are best known for making and maintaining dentin, not aiding perception. In odontoblasts, Dr Lennerz said, TRPC5 opens when the cold signal travels down the dentinal tunnels, causing a message to be sent to the nerves.

In this case, one 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 in doubt about the effectiveness of eugenol, if it relieves pain in some people, it may be because of its effect on TRPC5.

Perhaps knowing 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.

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