Odontoblasts, cells that form dentin, the shell beneath the tooth’s enamel that encases the soft dental pulp containing nerves and blood vessels, contain cold-sensitive proteins that detect temperature drops, according to a new study published in the journal Science Advances.
This artist’s illustration depicts how, centuries ago, people believed that small worms living within the tooth caused excruciating pain via their cold breath. Proof of tooth worms came when an inflamed tooth was ripped out and small stringy structures — the nerves and blood vessels — were visible within the disintegrating pulp and dentin. The tooth worms are actually odontoblasts, cells that form the dentin layer of the tooth, which encases the soft tooth pulp. Bernal et al. demonstrated that the cold sensation in our teeth is mediated by the odontoblast (green structures) and transmitted to the brain via nerves (red), where pain is perceived. Image credit: Katharina Zimmermann.
Insults to the tooth’s dentin produces inflammation, most commonly during tooth decay.
Dental caries is a chronic disease in which a bacterial biofilm on the tooth surface, in combination with fermentable carbohydrate substrates, causes demineralization and eventually tooth decay.
Worldwide, 2.4 billion people have an untreated caries in permanent teeth. Inflamed teeth are extremely cold sensitive, perceived as a short, sharp intense neuralgic pain.
“It’s a unique kind of pain. It’s just excruciating,” said co-corresponding author Dr. David Clapham, vice president and chief scientific officer of the Howard Hughes Medical Institute.
The researchers conducted experiments on mice whose molars were drilled under anesthesia.
The animals with dental injuries manifest pain with their behavior; they drink up to 300% more sugar water than their litter mates without dental injuries, for example.
By studying genetically altered mice that did not have the TRCP5 gene, they found that the mice with injured teeth did not manifest the increased drinking behavior and behaved like mice without dental injuries.
“We now have definitive proof that the temperature sensor TRCP5 transmits cold via the odontoblast and triggers nerves to fire, creating pain and cold hypersensitivity,” said co-corresponding author Dr. Jochen Lennerz, medical director of the Center for Integrated Diagnostics at Massachusetts General Hospital.
“This cold sensitivity may be the body’s way to protect a damaged tooth from additional injury.”
Specifically, in response to cold, the TRCP5 protein opens channels in the membrane of odontoblasts, enabling other molecules, such as calcium, to enter and interact with the cell.
If the tooth’s pulp is inflamed from a deep cavity, for example, TRCP5 is overabundant, causing increased electrical signaling via the nerves emerging from the root of the tooth and running to the brain, where pain is perceived.
When gums recede from aging, teeth can become hypersensitive because the odontoblasts are sensing cold in a newly exposed region of the tooth.
“TRPC5 makes cells more active in cold, and the odontoblasts’ ability to sense cold via TRPC5 makes this discovery so exciting,” Dr. Lennerz said.
The authors confirmed the presence of the TRPC5 protein in extracted human teeth, which was a technical tour de force.
They also identified a pharmacological target for minimizing tooth sensitivity to cold.
For centuries, oil of cloves has been used as a remedy for tooth pain. The active agent in oil of cloves is eugenol, which happens to block TRCP5.
Toothpastes containing eugenol are already on the market, but the team’s findings may lead to more potent applications to treat teeth that are hypersensitive to cold.
And there may be novel applications for eugenol, such as treating patients systemically for extreme cold sensitivity from chemotherapy.
“The main ingredient in clove oil, which has been used for centuries in dentistry, contains a chemical that blocks the ‘cold sensor’ protein,” said co-corresponding author Dr. Katharina Zimmermann, an electrophysiologist at the Friedrich-Alexander University Erlangen-Nürnberg.
“Developing drugs that target this sensor even more specifically could potentially eliminate tooth sensitivity to cold.”
“Once you have a molecule to target, there is a possibility of treatment.”
Laura Bernal et al. 2021. Odontoblast TRPC5 channels signal cold pain in teeth. Science Advances 7 (13): eabf5567; doi: 10.1126/sciadv.abf5567