Study reveals target for drug development for chronic jaw pain disorder

August 1, 2013
This is the cover of the August 2013 journal. Credit: This picture has been reproduced with permission of the International Association for the Study of Pain® (IASP).

Temporomandibular joint disorder (TMJD) is the most common form of oral or facial pain, affecting over 10 million Americans. The chronic disorder can cause severe pain often associated with chewing or biting down, and lacks effective treatments.

In a study in mice, researchers at Duke Medicine identified a protein that is critical to TMJD pain, and could be a promising target for developing treatments for the disorder. Their findings are published in the August issue of the journal Pain.

Aside from cases related to trauma, little is known about the root cause of TMJD. The researchers focused on TRPV4, an ion that allows calcium to rapidly enter cells, and its role in inflammation and pain associated with TMJD.

"TRPV4 is widely expressed in found in the trigeminal ganglion, which is responsible for all sensations of the head, face and their associated structures, such as teeth, the tongue and temporomandibular joint," said senior study author Wolfgang Liedtke, M.D., PhD, associate professor of neurology and at Duke. "This pattern and the fact that TRPV4 has been found to be involved in response to made it a logical target to explore."

The researchers studied both normal mice and mice genetically engineered without the Trpv4 gene (which produces TRPV4 channel protein). They created inflammation in the temporomandibular joints of the mice, and then measured bite force exerted by the mice to assess jaw inflammation and pain, similar to how TMJD pain is gauged in human patients. Given that biting can be painful for those with TMJD, bite force lessens the more it hurts.

The mice without the Trpv4 gene had a smaller reduction in bite force—biting with almost full force—suggesting that they had less pain. In normal mice there was more TRPV4 expressed in trigeminal sensory neurons when inflammation was induced. The increase in TRPV4 corresponded with a greater reduction in bite force.

The researchers also administered a compound to normal mice that blocked TRPV4, and found that inhibiting TRPV4 also led to smaller reductions in bite force, similar to the effects of the mice engineered without the Trpv4 gene.

Surprisingly, the researchers found comparable bone erosion and inflammation in the jaw tissue across all mice, regardless whether the mice had TRPV4 or not.

"Remarkably, the damage is the same but not the pain," Liedtke said. "The mice that had the most TRPV4 appeared to have the most pain, but they all had similar evidence of temporomandibular joint inflammation and bone erosion in the jawbone as a consequence of the inflammation."

The results suggest that TRPV4 and its expression in trigeminal sensory neurons contribute to TMJD pain in mice. Given the lack of effective treatments for this chronic pain disorder, TRPV4 may be an attractive target for developing new therapies.

Explore further: Scientists find molecular link to obesity and insulin resistance in mice

Related Stories

Scientists find molecular link to obesity and insulin resistance in mice

September 27, 2012
Flipping a newly discovered molecular switch in white fat cells enabled mice to eat a high-calorie diet without becoming obese or developing the inflammation that causes insulin resistance, report scientists from Dana-Farber ...

Jaw pain disorder tied to anxiety, depression

January 23, 2013
(HealthDay)—There's a link between depression and anxiety symptoms and temporomandibular joint (TMJ) disorder pain, a condition that affects the jaw, according to a new study.

Inflammatory on and off switch identified for allergic asthma and COPD

August 1, 2013
Japanese researchers have made a new step toward understanding why—and how to stop—runaway inflammation for both chronic obstructive pulmonary disorder (COPD) and allergic asthma. In a new report appearing in the August ...

Stopping cold: Scientists turn off the ability to feel cold

February 14, 2013
(Medical Xpress)—USC neuroscientists have isolated chills at a cellular level, identifying the sensory network of neurons in the skin that relays the sensation of cold.

Recommended for you

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.