Peripheral Anti-nociceptive and Anti-inflammatory Effect of Oleanolic Acid in a Rat Model of Osteoarthritis

Background: Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid with multifarious actions. The anti-inflammatory effect it exerts when taken orally is the most important; however, the underpinning mechanisms of such effects have not yet been fully explored. Methods: In the present study, we evaluated the anti-inflammatory and anti-nociceptive effect of OA by injecting it directly into the knee joint using an animal model of osteoarthritis. Behavioral and electrophysiological studies were conducted to determine whether OA exerts a direct modulatory effect on primary sensory afferents that can lead to a decrease in pain-related behaviors and inflammatory responses. Rats were divided into two main groups: a pre- and a post-treatment group. Knee joint inflammation was induced by injecting a mixture of 3% kaolin and carrageenan (K/C). In the pre-treatment group, two different doses of OA [5 mg/ml (n=5) and 30 mg/ml (n=4); 0.1 ml per injection] were administered into the synovial cavity of the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose [5 mg/ml (n=5)] of OA after induction of inflammation. Results: Results indicate that intra-articular injection of OA improves motor coordination and attenuates nociceptive behavior and inflammatory reactions. More importantly, we observed a direct depolarizing action of OA on articular sensory fibers, a crucial mechanism that activates descending inhibitory pathways and controls incoming nociceptive signals to the spinal cord. Conclusion: Overall, our findings suggest that OA can be used as a preventive and therapeutic approach for the management of osteoarthritis.