Abstract
Osteoarthritis (OA) is characterized by pain caused by inflammation and degradation of cartilage matrix in joint. Although the number of patients is expected to increase due to the aging of the population, the use of anti-inflammatory drugs, which is the main therapeutics, may not be effective in pathology of OA. REV-ERBs are one of nuclear receptors involved in a wide range of physiological functions. We have previously shown that REV-ERBs were expressed in primary cultured chondrocytes, and REV-ERB agonist suppresses the upregulation of proinflammatory cytokines and matrix degradation enzymes in these cells under inflammatory conditions. However, the role of REV-ERBs in pathogenesis of OA is not clear. Thus, we investigated the effect of REV-ERB agonist on nociceptive hypersensitivity in monoiodoacetate (MIA)-induced OA model. SR9009, a REV-ERB agonist, was administered intraarticularly twice a week, starting 3 days after MIA administration. Mechanical thresholds were measured by the von Frey test. MIA induced mechanical hypersensitivity from day 3 after administration, which persisted at least until day 28. Administration of SR9009 significantly ameliorated mechanical hypersensitivity from day 14 after MIA administration. These results suggest that activation of REV-ERB might induce an analgesic effect on OA pain.
