Comparison of effects of intra‐articular diclofenac etalhyaluronate and hyaluronic acid in a monoiodoacetate rat osteoarthritis model

Abstract

Diclofenac etalhyaluronate (DF‐HA) sustained diclofenac release with the effects of hyaluronic acid (HA), offering long‐term analgesia in osteoarthritis. In this study, the effects of DF‐HA on pain improvement and osteoarthritis were evaluated in a rat knee monoiodoacetate‐induced osteoarthritis model compared to HA. Eight rats per group had been injected with monoiodoacetate (2.0 mg) or saline in the right knee for 4 weeks and were injected with either DF‐HA (1.25 mg/kg; 0.5 mg), HA (0.5 mg), vehicle which was a substrate without DF‐HA (50 μL), or saline and followed for 4 weeks. Mechanical plantar skin sensitivity was assessed weekly using the von Frey assay. Osteoarthritis changes were monitored with Larsen scores via CT imaging at every 2 weeks. The articular cartilage was analyzed using OARSI scores through H&E, Safranin‐O staining at 8 weeks. The percentage of Iba‐1 positive microglia in the spinal dorsal horn and of FG + CGRP‐labeled cells among FG‐positive cells in the dorsal root ganglion were evaluated by immunohistochemical staining. TNF‐α and IL‐6 mRNA expression levels in the knee synovium were evaluated by PCR. The DF‐HA showed significantly improved pain hypersensitivity compared with the HA at 6–8 weeks. The percentage of Iba‐1‐positive microglia was significantly lower than that in the vehicle and the percentage of FG + CGRP/FG was significantly lower than that in the HA. OARSI scores did not differ among treatment groups, Larsen scores indicated lower in the DF‐HA than in the vehicle. DF‐HA was as effective as HA in joint protection and significantly improved inflammatory pain compared to HA.