Abstract Rheumatoid arthritis (RA) is an inflammatory disease that utilizes nonbiologic and biologic drugs for appropriate disease management. However, high cost, adverse effects, reduced effectiveness, and risk of infection have stimulated the search for safer and more efficacious therapeutic strategies. In the present study, we aimed to evaluate the anti-inflammatory and analgesic properties of eucalyptol in an experimental model of arthritis. Mice were administered zymosan or saline intra-articularly. One hour before the zymosan administration, the mice were treated with oral eucalyptol (200-400 mg/kg) and vehicle. Cell influx, neutrophils, lymphocytes, and monocytes were measured in joint exudates. Joint pain was assessed using paw-pressure tests. Orally administered eucalyptol (200 and 400 mg/kg) significantly reduced cell influx, as well as neutrophils, lymphocytes, and monocytes, when compared with the control. Eucalyptol at a dose of 400 mg/kg significantly reversed joint pain and demonstrated analgesic activity (60%); however, 200 mg/kg failed to alter joint pain. These results indicate that oral eucalyptol promotes anti-inflammatory and analgesic activity in mice subjected to zymosan-induced arthritis.

Abstract Background: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. Methods: Mice received 100 μg/25 μL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. Results: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. Conclusion: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.