A team of researchers from Boston University have uncovered a new
function for odontoblasts, the cells that form dentin, the shell beneath
the tooth's enamel that encases the soft dental pulp containing nerves
and blood vessels.
The results of the study were published in the journal of Science Advances.
"We
found that odontoblasts, which support the shape of the tooth, are also
responsible for sensing cold," says pathologist Jochen Lennerz, MD,
PhD, one of the paper's senior authors and 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."
Teeth
that hurt from exposure to cold can occur for many reasons. Many people
have experienced intense pain from cold when they have a hole in a
tooth from an untreated cavity, for example. But teeth can also become
very sensitive to cold from gum erosion due to aging. Some cancer
patients treated with platinum-based chemotherapies have extreme cold
sensitivity all over their bodies. "A breeze on the face registers as
extreme pain in the teeth, which may even cause some patients to stop
therapy," says Lennerz.
Tooth pain has been notoriously difficult to study. A tooth's
hardness makes it a challenging tissue to study and inducing tooth pain
in humans requires opening the tooth. The team of researchers,
therefore, conducted experiments on mice whose molars were drilled under
anaesthesia. Mice with dental injuries manifest pain with their
behaviour; they drink up to 300 per cent more sugar water than their
littermates without dental injuries, for example. In previous research,
the team of investigators had discovered TRCP5, a protein encoded by the
TRCP5 gene that is expressed in nerves in many parts of the body. Their
earlier discovery allowed the researchers to zero in on TRCP5 as a
mediator of pain from cold.
By studying genetically altered mice
that did not have the TRCP5 gene, the researchers found that the mice
with injured teeth did not manifest the increased drinking behaviour 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," says Lennerz. "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 ageing, teeth can become
hypersensitive because the odontoblasts are sensing cold in a newly
exposed region of the tooth. "Most cells and tissues slow their
metabolism in the presence of cold, which is why donor organs are put on
ice," says Lennerz. "But TRPC5 makes cells more active in cold, and the
odontoblasts' ability to sense cold via TRPC5 makes this discovery so
exciting."
Lennerz confirmed the presence of the TRPCS protein in extracted
human teeth, which was a technical tour de force. "Our teeth aren't
meant to be cut into ultra-thin layers so they can be studied under the
microscope," says Lennerz, who first had to decalcify the teeth and put
them in epoxy resin before slicing them and identifying the TRPC5
channels in the odontoblasts.
The research team 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 the oil of cloves is eugenol, which happens to block
TRCP5. Toothpaste containing eugenol are already on the market, but the
findings of this study 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. "I'm excited to see how
other researchers will apply our findings," says Lennerz.