Electrophysiological evidence that the vasoactive intestinal peptide receptor antagonist VIP6-28 reduces nociception in an animal model of osteoarthritis

Objective: The present study examined whether local administration of the neuropeptide vasoactive intestinal polypeptide (VIP) could modulate joint nociception in normal rat knee joints and if the VIP antagonist VIP6-28 could ameliorate joint mechanosensitivity in an animal model of osteoarthritis (OA). Methods: OA was induced in male Wistar rats by intra-articular injection of 3 mg sodium mono iodo-acetate with a recovery period of 14 days. Electrophysiological recordings were made from knee joint primary afferents in response to normal rotation and noxious hyper-rotation of the joint both before and following close intra-arterial injection of different doses of VIP and VIP6-28. Results: Local application of VIP to normal knees caused afferent firing rate to be significantly enhanced during normal rotation (up to 180% P < 0.01; n = 17) and during hyper-rotation (up to 37% P < 0.01; n = 17) of the knee. VIP-induced sensitization was blocked by pre-administration of the VIP receptor antagonist VIP6-28. In the OA group, application of VIP6-28 caused afferent firing rate to be significantly reduced during normal rotation (up to 45% P < 0.05; n = 17) and during hyper-rotation (up to 34% P < 0.01; n = 15) of the knee joint. Conclusion: These findings indicate that VIP is involved in peripheral sensitization of knee joint afferents especially in response to normal joint movements. OA-incluced sensitization of knee joint afferents was inhibited by local administration of VIP6-28, indicating that VIP is released into CA knee joints, potentially contributing to joint pain. As such, VIP6-28 may prove to be a beneficial agent for the treatment of arthritis pain. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.