Peripheral anti-nociceptive effect of oleanolic acid in a rat model of osteoarthritis

Abstract

Osteoarthritis, the most common form of joint inflammation, is characterized by severe pain and hypersensitivity to thermal and mechanical stimulation, and by prolonged increase in the synaptic excitability of central nociceptive neurons. Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid present in food and plants, is thought to play a beneficial role in inflammation owing to its neuroprotective effects. OA modulates several nuclear receptors involved in regulating bile acid through the activation of transcription factors. Converging evidence has pointed towards a role for OA and these receptors in the regulation of inflammation. However, despite significant progress in research, the role of OA in anti-nociception and anti-inflammation is still not fully understood. In this study, we hypothesize that Oleanolic acid exerts an anti-nociceptive and anti-inflammatory effect in a rat model of osteoarthritis. To test this hypothesis, we conducted behavioral and electrophysiological studies to examine the effect of intra-articular OA on the development of nociceptive behaviors, knee joint edema formation, motor incoordination and increased afferent discharges associated with knee joint inflammation. Materials and Methods: Knee joint Inflammation was induced by injecting a mixture of 3percent kaolin and carrageenan (K-C). Sensory and motor tests were performed in rats prior to, and at 4, 8, 24, 48 and 168hrs following the induction of inflammation. The knee joint circumference was measured, at each time point, to monitor the development of joint edema. Rats were divided into two main groups: Pre-treatment and post-treatment. In the pre-treatment groups, two different doses of OA (0.5mg (n=5) and 3mg(n=4)) were administered in the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose (0.5mg g (n=5)) of OA after induction of inflammation. The control groups received a solution of 100percent ethanol, as a vehicle substance. Nociceptive behaviors were assessed in all an