As many TMD patients know, it often hurts to bite down hard on foods, so they resort to a soft diet and less strenuous bite forces when their TMD pain kicks in. Now, a team of investigators led by Dr. Wolfgang Liedtke at Duke University Medical Center in Durham, NC have taken advantage of that observation to detail changes in the brain that can account for that reduced biting force.
Using a mouse model, they injected a chemical compound into the TM joint that is well known to generate joint inflammation and associated pain. The animals were then injected with either an NSAID or a TRPV4 inhibitor. Dr. Liedtke suspected that the protein, TRPV4, found on the surface of sensory nerve cells in the trigeminal ganglion of the brain (which supplies the TM joint) might be critical. He had discovered the protein in the year 2000 and noted its involvement in response to mechanical stimulation and also in response to pain and inflammation.
TRPV4 is an ion channel, which, when activated, allows calcium to enter a nerve cell, exciting it to fire an electric charge. It turns out that in response to joint inflammation and pain, not only was there increased expression of the TRPV4 ion channels on sensory neurons in the brain in parallel with the severity of inflammation and pain, but when the mice were tested using a bite force measuring apparatus, they showed a reduction in bite force in comparison with controls.
In contrast, when the mice were injected with an agent that blocked TRPV4 ion channels, the biting forces returned to more normal levels. As a further test of the key role of the TRPV4 channel, the Duke team tested mice genetically engineered to lack the gene (called TRPV4) that codes for the protein. These mice also were resistant to the effects of TM inflammation on bite force. The researchers also determined that the presence of TRPV4 had the effect of re-programming the trigeminal ganglion to be more “pro-pain” and also acted as a “switch-on”mechanism in pain-sensing neurons in the ganglion.
The bottom line is that the TRPV4 protein appears to be an attractive target for the development of new drugs to treat TMD.
Source: Chen Y, Williams SH, McNulty AL, Hong JH, Lee SH, Rothfusz NE, Parekh PK, Moore C, Gereau RW 4th, Taylor AB, Wang F, Guilak F, Liedtke W., Temporomandibular joint pain: A critical role for TRPV4 in the trigeminal ganglion, Pain.2013 Aug;154(8):1295-304.