This article is from WeChat official account:Principle (ID: principle1687), author: TakeNeko, from the head of FIG: “cat and mouse”, original title: “҉҉҈ cold cold cold ҉҉҈ ҉҉҈ pain ྂ pain ྂ pain ྂ”

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“Hey!”

“Oh Yo Yo Yo Yo…” (cover your left face)

“Goooooooooooooo…”

“uh ah ah ah ah ……” (the right cheek hold)

For people with decayed or extremely sensitive teeth, these scenes may remind you of the unique painful torture-when you bite a popsicle, when you eat a cold drink, you can’t be the first It may be fragile teeth.

Tooth decay occurs when bacteria and acid erodes the enamel (hard white tissue on the surface of the tooth). After the enamel is eroded, cavities will form in the teeth. It is estimated that about 2.4 billion people in the world have untreated cavities in their permanent teeth. This number accounts for about one-third of the world’s population. This can cause severe pain and make the teeth extremely sensitive to cold.

Although scientists have proposed a major hypothesis to explain these problems, no one really understands how the teeth feel cold. The thin tubes inside the teeth contain liquid, and when the temperature changes, the liquid moves. Some scientists believe that nerves can sense the direction of this movement in a certain way, which can signal whether the tooth is cold or hot. However, people cannot rule out this theory, but they have not yet found any direct evidence to support this claim.

Now, an international scientific team has finally solved the mystery of tooth perception of cold and determined the molecular and cellular factors behind it.The team published a paper in the recent “Science Advances” report, in mice and humans, in a type of tooth cells called odontoblasts, contain cold-sensitive proteins that can sense a drop in temperature. These signals from cells will eventually cause significant pain.

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The beginning of this research can actually be traced back more than ten years ago. At that time, Katharina Zimmermann, one of the corresponding authors of the new study, was conducting postdoctoral research. Together with her team, she discovered an ion channel called TRPC5.

Ion channels can be understood as a kind of “small holes” similar to molecular gates in the cell membrane. When a signal is detected, such as when chemical information is received, or a temperature change is sensed, such channels will either be closed tightly or opened to allow ions to flood into the cell. This creates a rapid electrical impulse from one cell to another. This is a way to transmit information quickly and is essential for the brain, heart, and other tissues.

Scientists have realized that the TRP channel family is very important for animal temperature perception, this family is very old in the evolutionary history, for example, TRPV1 can be activated by high temperature and capsaicin(For details, please refer to “Why do we have chrysanthemum pain?”), TRPM8 will react to menthol and cold.

The TRP family is a very important type of ion channel, which is very important for temperature perception. The most famous members include TRPV1, TRPM8, etc. | Image source: kavliprize.org

At the time, Zimmermann and his team discovered that TRPC5 was extremely sensitive to cold. But what the team doesn’t know is that TRWhat part of the body does this cold-sensing ability of PC5 work? They found that the answer does not seem to be as simple as skin.

In Zimmermann’s words, the subsequent research seemed to “reach a dead end.” Until one day, the team was sitting together, having lunch, discussing this issue, and thinking about where else in the body could feel cold. They thought of teeth.

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As we all know, teeth are not an easy object to study. The teeth are very hard. For example, if you want to study toothache, a scientist may have to cut through the two layers of enamel and dentin, which are very hard materials, without destroying the soft pulp of the tooth and its internal blood vessels and nerves. Many experienced researchers know that in actual operation, sometimes the entire tooth will “split”.

The new research team designed a new experiment on mice. They did not open the mouse’s teeth and only examined the cells in them. Instead, they chose to study the entire system, including jaws, Teeth and dental nerves.

The team recorded the nerve activity of the entire system when the cold solution touched the tooth. In normal mice, this cold triggers nerve activity, indicating that the teeth feel cold. But this is not the case in mice that have been genetically modified to lack TRPC5, or in mice whose teeth have been treated with a chemical that blocks ion channels. This is a key clue that ion channels can sense cold.

In mouse molars, odontoblasts containing ion channels TRPC5 (green) are tightly packed in the area between the dental pulp and dentin. The long whisker-like extension of the cell fills the thin tubes in the dentin that extend to the enamel. | Picture source: L. Bernal et al./Science Advances2021

They tracked the location of TRPC5 and found that it is located in a specific cell type, which is called odontoblasts, located between the pulp and dentin. In addition, they noticed that another TRP ion channel, TRPA1, seemed to play a role in it.

At the same time, pathologist Jochen Lennerz used superb experimental technology to confirm after examining human tooth samples that TRPC5 does exist in human teeth, as well as in teeth with cavities.

Lennerz believes that this discovery is very exciting, “Most cells and tissues will slow down their metabolic activity in a cold environment, but TRPC5’does the opposite’ and makes cells more active in the cold.” . Confirming that odontoblasts can perceive cold through the TRPC5 channel also uncovered a mystery that has puzzled scientists for a long time.

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Although toothache is not a “hot” research topic, it is actually very important because it affects almost everyone.

After finding this key ion channel, it is hoped that in the future, it will be possible to develop drugs for this receptor, which can more specifically reduce the sensitivity of teeth to cold. In more “scientific” terms, once a molecule is found as a “target”, the corresponding treatment is possible.

This study actually explains how an ancient home remedy relieves toothache. For centuries, clove oil (clove oil) has been a common substance in dental treatment. In fact, the main components of clove oil contain one A chemical substance can block this cold-sensitive protein molecule.

For Zimmermann, this research spanned more than ten years. She mentioned: “It is extremely difficult to figure out the functions of specific molecules and cells. High-quality research may take a long time.”

#Reference source:

https://www.hhmi.org/news/how-teeth-sense-the-cold

https://www.eurekalert.org/pub_releases/2021-03/mgh-rdw032621.php

https://advances.sciencemag.org/content/7/13/eabf5567/tab-article-info

This article is from WeChat official account:Principle (ID: principle1687), author: TakeNeko