Application of in vivo siRNA Techniques in TMJ Pain

Altering gene expression to control temporomandibular joint (TMJ) pain without side effects has not been reported and there is no report describing the use of small interfering RNA (siRNA) to modulate gene expression in the TMJ to block TMJ pain. We hypothesize that siRNA is a potential therapeutic approach for treating TMJ pain and a method for rapid, in vivo validation of newly identified therapeutic targets. siRNA that targets the Fc receptor gamma RIII (FcγRIII) gene was injected into the TMJ and the effect on joint morphology and the pain response resulting from inflammatory arthritis was measured. FcγRIII was selected as a target because it is a receptor restricted to leukocytes and was found at high concentrations in synovial tissue impacted by arthritis, including TMJ tissues. Injection of FcγRIII siRNA concomitant with induction of TMJ arthritis (15 µg CFA) significantly (p<0.001) reduced the pain response by 50% 2 days post injection in comparison to rats receiving control siRNA. This reduction in pain was concomitant with high levels of FcγRIII siRNA in the TMJ tissues and reduced FcγRIII expression in the TMJ tissues, suggesting attenuation of FcγRIII gene expression was associated with the reduced pain in a rat with an arthritic TMJ. Also, injection of the control siRNA in five rats had no effect on the pain induced by TMJ inflammation in comparison to four rats that received just vehicle suggesting that the siRNA in and of itself does not affect the inflammatory pain response through non-specific binding of the Toll-like receptor 3 inhibiting angiogenesis. Moreover, siRNA and decreased levels of FcγRIII expression did not alter joint morphology. These studies demonstrate that blockade of the FcγRIII gene using siRNA attenuated TMJ pain in a rat model suggesting the therapeutic efficacy of siRNA in ameliorating TMJ pain.