Temporomandibular joint disorder (TMJD) is characterized by severe jaw pain associated with chewing or biting down. There is no effective treatment for the disorder, which affects more than 10 million Americans. TMJD can arise from trauma, but for many cases, the underlying cause is not known, hindering attempts to develop therapeutic strategies. A study by researchers at Duke University (Durham, NC) has now identified a protein that is required for TMJD-associated pain in mice. The protein, TRPV4, may be a new target for pain relief in TMJD.

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TRPV4 is an ion channel protein that allows calcium to rapidly enter cells. It is known to be involved in both inflammation and mechanically evoked pain. Wolfgang Liedtke, who led the study, explained why his team focused on TRPV4. “TRPV4 is widely expressed in sensory neurons 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,” he said in a press release. “This pattern and the fact that TRPV4 has been found to be involved in response to mechanical stimulation made it a logical target to explore.”

Liedtke's team compared normal mice with mice in which the gene encoding TRPV4 was ablated so that the protein could not be expressed. They injected complete Freund's adjuvant bilaterally into the TMJs of the mice to create inflammation as a model of TMJD and measured the bite force exerted by the mice. Because bite force lessens as TMJ pain increases, bite-force attenuation is a suitable proxy for assessing TMJD-like pain in the mice.

Mice lacking TRPV4 had less bite-force attenuation than did normal mice, suggesting that they had less pain. Additionally, in normal mice, TRPV4 expression in trigeminal sensory neurons was greater when inflammation was induced, and this increase in TRPV4 corresponded with greater bite-force attenuation. Furthermore, blockade of TRPV4 expression in normal mice led to reduced bite-force attenuation, similar to that observed in mice lacking TRPV4 (Pain 154, 1295–1304; 2013).

These results suggest that TRPV4 contributes to TMJD-like pain in mice. But lack of TRPV4 does not appear to prevent TMJD-related damage. Bone erosion and jaw inflammation were comparable in normal mice and mice lacking TRPV4. “Remarkably, the damage is the same but not the pain,” Liedtke said.

Nevertheless, approaches to block TRPV4 may prove useful in treating the pain associated with TMJD.