HMS Affiliates Help Publish Novel Study on Causes of Cold-Induced Tooth Pain


A group of researchers from around the world, including two Harvard Medical School affiliates, discovered a new cellular function that explains how teeth sense cold temperatures and why that causes tooth pain.

The team published a paper titled “Odontoblast TRPC5 channels signal cold pain in teeth” in the journal Science Advances on March 26 that revealed a novel function for odontoblast cells in the tooth. According to the researchers, these findings are an important breakthrough from a basic science standpoint and can be applied to help relieve cold-induced pain in patients.

The two Medical School affiliates who worked on the study are Professor of Cardiovascular Research emeritus David E. Clapham and Associate Professor of Pathology Jochen K. Lennerz.

Katharina Zimmermann, a co-author of the paper and researcher at Friedrich Alexander University of Erlangen-Nuremberg in Germany who specializes in the study of pain, explained how enamel and dentin — outer layers of the tooth that work in tandem to protect the inner layers that contain blood vessels and nerve cells — are some of the most important structural components in teeth.


Researchers previously believed tooth pain was caused by the expansion and contraction of a fluid inside the dentin shell. This theory argued that the movement of the fluid pressed on nerve endings situated near the shell.

“The problem is that there has never been a model, either a biomechanical or another experimental model, that would have allowed to measure any of these mechanical forces that were postulated,” Zimmermann said.

Lennerz, who also serves as medical director at Center for Integrated Diagnostics at Massachusetts General Hospital, discovered that a protein named TRPC5 — which the team predicted played a role in cold sensing — was actually present in large quantities in nerve cells in teeth. After stimulating pain receptors in mice teeth and gathering signals from those nerve cells, they found TRPC5 in large amounts in odontoblasts.

The findings suggested TRPC5 is actually active in the odontoblasts, rather than in the nerves as previously thought.

A possible application of the study’s findings could be alleviating pain for individuals with hypersensitive teeth. Oil of cloves, otherwise known as eugenol, has long been used to treat tooth pain caused by cold temperatures. Until now, however, nobody understood why.

Lennerz explained eugenol works by inhibiting TRPC5 currents and disrupting the cold transduction pathways.

In addition to expanding product lines that use eugenol, understanding these mechanisms makes it easier to develop solutions to other related problems that are ripe areas for future research, according to Lennerz.

“It clarifies this ancient myth about what causes that pain,” he said. “I think it illustrates that this pain, this suffering related to a tooth has been a long standing problem and any puzzle piece to add to our understanding of that is, at least to me, super exciting.”