How teeth sense the cold

The Howard Hughes Medical Institute’s vice president and chief scientific officer, David Clapham, describes the agony as “a distinct type” (HHMI). This is painful, as she put it. Researchers from across the world have now discovered how teeth detect cold, and they’ve narrowed their search to molecules and cells. The team reveals in Science Advances on March 26th, 2021 that tooth cells called odontoblasts have cold-sensitive proteins that sense temperature changes in both mice and humans. These cells’ signals may eventually cause a shock of pain in the brain. The article explains how an old-fashioned home treatment for toothaches works. According to German electrophysiologist Katharina Zimmermann, the primary component in clove oil, which has been used in dentistry for millennia, includes a molecule that inhibits the “cold sensor”protein.

Zimmermann believes that by finding medicines that particularly target this sensor, teeth sensitivity to cold may be eradicated. “Treatment is possible once you have a molecule to target.” Teeth decay occurs when the enamel, the tooth’s hard, white coating, is eaten away by films of bacteria and acid. Cavities develop as the enamel on your teeth erodes. Untreated cavities in permanent teeth affect 2.4 billion individuals, or approximately a third of the world’s population, and may cause severe discomfort, including acute sensitivity to cold. Although scientists had offered one major hypothesis, no one truly understood how teeth felt cold. The fluid within the teeth’s canals flows in response to variations in temperature. In some mysterious way, the direction of movement is perceived by nerves as a signal of the temperature of a tooth.

Clapham, a neurobiologist at HHMI’s Janelia Research Campus, says, “We can’t rule this idea out,” but he adds that there was no evidence to support it. Studying tooth fluid flow, as well as dental biology in general, is challenging. Researchers must cut through the tooth’s enamel (the toughest material in the body) and another strong layer known as dentin without crushing the pulp’s soft tissue or the blood vessels and nerves that are located there. Occasionally, Zimmermann adds, “the whole tooth may just crumble into little fragments. It was not the intention of Zimmerman, Clapham, and their colleagues to examine teeth. Cell membrane holes called ion channels function as molecular gates in their research. The channels either clamp down or open wide when they detect a signal — such as a chemical message or a change in temperature. As a result, an electrical pulse is generated, and it travels from cell to cell at breakneck speed. In the brain, heart, and other tissues, it’s critical for transmitting information quickly.

Clapham’s group found an ion channel called TRPC5 was very sensitive to cold around fifteen years ago while Zimmermann was a postdoc there. However, the team was baffled as to where TRPC5’s cold-sensing capacity existed in the body. When they dug further, they discovered it wasn’t even the skin. In 2011, the researchers published in the journal Proceedings of the National Academy of Sciences that mice without an ion channel could nevertheless feel cold. Zimmermann claims that after it, “we came to a dead end”. The light bulb went out one day while the crew was having lunch and discussing the issue. ” So what other tissues in the body can feel the cold, David wondered aloud.” Zimmermann has a distinct memory of this. The solution was in the form of incisors.

To his surprise, pathologist Jochen Lennerz of the Massachusetts General Hospital found TRPC5 to be present in human adult teeth, particularly in those with cavities. He discovered this after looking at samples from human adults. Researchers were persuaded by a new mouse experiment that TRPC5 does indeed serve as a cold sensor. Zimmermann’s team examined the whole system, including the jawbone, teeth, and tooth nerves, rather than just a single sample. When an ice-cold solution was applied to the tooth, the researchers were able to capture brain activity. It was found that freezing a mouse’s teeth stimulated nerve activity, which indicated that the tooth was responding to the cold. This wasn’t the case with animals deficient in TRPC5 or in teeth treated with a substance that inhibited the ion channel’s function. Ion channels can sense cold, according to Zimmermann’s findings. In addition to TRPA1, the researchers found evidence that additional ion channels may have had a part in the disease process as well. The researchers found TRPC5 in the odontoblast, a cell type found at the pulp-dentin junction. A “ow!” signal is sent to the brain when someone with a dentin-exposed tooth bites down on a popsicle and those TRPC5-packed cells detect the chilly feeling.

Clapham claims that despite its importance, the acute sensation has received less research attention compared to other scientific fields. He acknowledges that tooth discomfort isn’t the hottest topic right now, but insists that “it is significant and impacts a lot of people.” A decade of research went into finding this answer, as Zimmermann points out. Identifying the function of individual molecules and cells, according to her, is a tough task. It takes time to do thorough research, as well.

Journal Reference: Laura Bernal, Pamela Sotelo-Hitschfeld, Christine König, Viktor Sinica, Amanda Wyatt, Zoltan Winter, Alexander Hein, Filip Touska, Susanne Reinhardt, Aaron Tragl, Ricardo Kusuda, Philipp Wartenberg, Allen Sclaroff, John D. Pfeifer, Fabien Ectors, Andreas Dahl, Marc Freichel, Viktorie Vlachova, Sebastian Brauchi, Carolina Roza, Ulrich Boehm, David E. Clapham, Jochen K. Lennerz, Katharina Zimmermann. Odontoblast TRPC5 channels signal cold pain in teethScience Advances, 2021; 7 (13): eabf5567 DOI: 10.1126/sciadv.abf5567

Categories: Dental