MAR 28, 2021 7:51 AM PDT

Understanding How Cold-Induced Tooth Pain Happens

WRITTEN BY: Carmen Leitch

Our teeth do a lot of work, and they may become sensitive to cold as the gums erode due to aging or because they have an untreated cavity (another reason why taking proper precautions and proactively seeking the correct dental treatments is important).. Cancer patients receiving chemotherapies that utilize platinum may also become extremely sensitive to cold in general. Scientists have now learned more about cells called odontoblasts that give rise to a shell underneath the enamel of teeth called dentin. Dentin contains dental pulp, where there are nerves and blood vessels. The findings have been reported in Science Advances.

Image credit: Piqsels

"We found that odontoblasts, which support the shape of the tooth, are also responsible for sensing cold," said one of the co-senior study authors, pathologist Jochen Lennerz, M.D., Ph.D., medical director of the Center for Integrated Diagnostics at Massachusetts General Hospital (MGH). "This research contributes a new function to this cell, which is exciting from a basic-science standpoint. But we now also know how to interfere with this cold-sensing function to inhibit dental pain."

Oxaliplatin is a chemotherapy drug that may cause cold dysesthesia, and this cold sensitivity can be severe. "A breeze on the face registers as extreme pain in the teeth, which may even cause some patients to stop therapy," Lennerz explained.

It's been challenging to study pain in the teeth in part because teeth are so hard; the tissue is difficult to sample. In this research, a mouse model was used in which their molars were drilled under anesthesia, which causes them to drink 300 percent more sugar water than mice without drilled molars. Previous work has indicated that TRPC5, a gene that expresses the TRPC5 protein in many nerves, is involved in the sensation of pain caused by cold.

When mice lack a TRPC5 gene, they do not exhibit the same excessive drinking behaviors when their molars are drilled.

"We now have definitive proof that the temperature sensor TRPC5 transmits cold via the odontoblast and triggers nerves to fire, creating pain and cold hypersensitivity," said Lennerz. "This cold sensitivity may be the body's way to protect a damaged tooth from additional injury."

When stimulated by cold, TRPC5 opens channels in odontoblast membranes. When these channels open, other molecules including calcium enter the cell and cause other effects. Inflammation caused by cavities increases the level of TRPC5, so the signaling from the inflamed tooth to the brain is increased. When gums recede as we age, odontoblasts may begin sensing pain in newly exposed areas. Therefore, in both situations, the brain feels more pain when the tooth experiences cold.

"Most cells and tissues slow their metabolism in the presence of cold, which is why donor organs are put on ice," said Lennerz. "But TRPC5 makes cells more active in cold, and the odontoblasts' ability to sense cold via TRPC5 makes this discovery so exciting."

The scientists also connected the old-fashioned tooth-pain remedy of clove oil to TRPC5; the active ingredient in clove oil is eugenol, which can block TRPC5. Though some toothpaste is made with eugenol, this research suggests that it could be useful in more potent forms as a treatment for severe cold sensitivity, such as what cancer patients on platinum compounds experience.

"I'm excited to see how other researchers will apply our findings," said Lennerz.

Sources: AAAS/Eurekalert! via Massachusetts General Hospital, Science Advances

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 14, 2021
Genetics & Genomics
RSV Infections Can Modify Host Immune Gene Activity
OCT 14, 2021
RSV Infections Can Modify Host Immune Gene Activity
Respiratory syncytial virus (RSV) are thought to be incredibly common; research has suggested that almost everyone is ev ...
OCT 18, 2021
Cell & Molecular Biology
Learning More About the Molecular Basis of Appetite
OCT 18, 2021
Learning More About the Molecular Basis of Appetite
Neurons in the human brain play a crucial role in appetite, satiety, and metabolism. Research has revealed more about th ...
OCT 18, 2021
Genetics & Genomics
A Decade After Gene Therapy, SCID Patients Are Doing Well
OCT 18, 2021
A Decade After Gene Therapy, SCID Patients Are Doing Well
For decades, scientists have been trying to find ways to cure disorders that can be traced back to an error in one gene. ...
OCT 28, 2021
Clinical & Molecular DX
Asthma Diagnostic Detects Leaky Airways
OCT 28, 2021
Asthma Diagnostic Detects Leaky Airways
Both asthma and chronic obstructive pulmonary disease (COPD) are airway disorders associated with elevated, uncontrolled ...
NOV 16, 2021
Cell & Molecular Biology
Modeling the Separation of Liquids in Cells
NOV 16, 2021
Modeling the Separation of Liquids in Cells
Oil and water are both liquids, but they don't mix well, demonstrating a phenomenon known as liquid-liquid phase separat ...
DEC 02, 2021
Microbiology
A 'Bispecific Antibody' to Fight Crimean-Congo Hemorrhagic Fever
DEC 02, 2021
A 'Bispecific Antibody' to Fight Crimean-Congo Hemorrhagic Fever
Crimean-Congo hemorrhagic fever (CCHF) is a deadly disease, which is fatal in about 30 percent of cases. It's caused ...
Loading Comments...