Our result showed that the expression of IL- 1b, IL-6 and iNOS were reduced with CoQ10 treatment, potentially explaining the reduced secondary tactile allodynia measured by von Frey hair test in our model. With the lack of MCE Company 821768-06-3 direct and LY333328 diphosphate standardized test which can reflect the pain severity in OA animal model, von Frey hair test has been used as a painestimating procedure. Nevertheless, as it cannot distinguish between pain and simple mechanically annoying stimuli, the results should be interpreted prudently. In our study, the reduced secondary tactile allodynia was accompanied by decreased expression of pain-generating cytokines in the arthritic joints, supporting that the results of Frey test reflected the pain severity. The antinociceptive effect of CoQ10 has been widely accepted in treating statin-induced myalgia. Recently, it was also shown to be effective in headache of fibromyalgia patients. The authors argued that the pain in these diseases was associated with mitochondrial dysfunction, which could be restored by CoQ10 supplement. Provided that mitochondrial dysfunction has also been implicated in OA pathogenesis, CoQ10 may reduce the OA pain through a similar mechanism. MIA, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, was used to induce OA like lesion in rat joints as it causes cartilage degradation resembling the pathological changes of human OA. Similar to the implication of ROS and mitochondrial dysfunction in human OA, MIA-induced chondrocyte apoptosis was recently reported to be mediated by the mitochondrial pathway involving ROS production and caspase activation. This findings further support that the MIA model can represent human OA as it shows similar mechanism of cartilage degradation. In our rat OA model, CoQ10 appears to have abrogated MIA-induced mitochondrial dysfunction and contributed to pain reduction. As well, our result showed that the expression of iNOS was reduced after CoQ10 treatment in OA joints. The increased iNOS expression reflects the increased NO in the OA joints. The role of NO in the pathogenesis of OA has been recently described in detail. The most renounced role of NO is mediated by peroxynitrite, which is generated by combination of NO and ROS. Peroxynitrite induces tissue oxidative damage and apoptosis of chondrocytes. Moreover, NO itself is associated with subchondral bone sclerosis, which has emerged as critical in OA pathogenesis in terms of bone r
