(626): Hylan G-F 20 attentuates knee pain in rat model of osteoarthritis

Abstract

Osteoarthritis (OA) is joint disease characterized by progressive degeneration of articular cartilage and development of chronic pain. Although a clinical benefit of hyaluronic acid (HA) has been demonstrated in patients, the mechanisms underlying this therapeutic benefit remain elusive. Therefore, the objective of this study was to measure pain behaviors in a rat model of surgically-induced OA and utilize the model to evaluate the analgesic efficacy of hylan G-F 20 (cross-linked HA) for its ability provide pain relief. Previous studies in our laboratory have demonstrated histological evidence of OA lesions following menisectomy (MSX). Analysis of mechanical allodynia revealed significant increases in sensitivity that began within 72 hours post-surgery and persisted over the entire course of the experimental period. Morphine was able to reverse allodynia at each time point providing evidence that this behavior was pain related. Two weeks following OA induction the animals were treated by intra-articular injection of hylan G-F 20 (once a week for 3 weeks) or steroid (once) and tactile allodynia measured on day 3, 10, 15, 22, 29, 36, 43 and 50. Both IA treatment reversed allodynia on days 22, 29, 36, 43 and 50 following treatment. The study demonstrates ability of Hylan G-F 20 to provide pain relief comparable to that seen with steroid. OA pain is a complex process involving both peripheral and central sensitization. HA has been used to treat OA pain but its mechanism of action remains elusive. This is partly due to lack of animal models to evaluate pain in osteoarthritis. We have reproduced and employed rat models of OA pain to evaluate analgesic properties of HA. This result suggests that this model could provide us with a tool to understand how HA influences the molecules involved in induction and maintenance of chronic arthritic pain and evaluating drugs for relieving OA pain. Osteoarthritis (OA) is joint disease characterized by progressive degeneration of articular cartilage and development of chronic pain. Although a clinical benefit of hyaluronic acid (HA) has been demonstrated in patients, the mechanisms underlying this therapeutic benefit remain elusive. Therefore, the objective of this study was to measure pain behaviors in a rat model of surgically-induced OA and utilize the model to evaluate the analgesic efficacy of hylan G-F 20 (cross-linked HA) for its ability provide pain relief. Previous studies in our laboratory have demonstrated histological evidence of OA lesions following menisectomy (MSX). Analysis of mechanical allodynia revealed significant increases in sensitivity that began within 72 hours post-surgery and persisted over the entire course of the experimental period. Morphine was able to reverse allodynia at each time point providing evidence that this behavior was pain related. Two weeks following OA induction the animals were treated by intra-articular injection of hylan G-F 20 (once a week for 3 weeks) or steroid (once) and tactile allodynia measured on day 3, 10, 15, 22, 29, 36, 43 and 50. Both IA treatment reversed allodynia on days 22, 29, 36, 43 and 50 following treatment. The study demonstrates ability of Hylan G-F 20 to provide pain relief comparable to that seen with steroid. OA pain is a complex process involving both peripheral and central sensitization. HA has been used to treat OA pain but its mechanism of action remains elusive. This is partly due to lack of animal models to evaluate pain in osteoarthritis. We have reproduced and employed rat models of OA pain to evaluate analgesic properties of HA. This result suggests that this model could provide us with a tool to understand how HA influences the molecules involved in induction and maintenance of chronic arthritic pain and evaluating drugs for relieving OA pain.