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

SummaryObjectiveThe 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).MethodsOA was induced in male Wistar rats by intra-articular injection of 3 mg sodium monoiodo-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.ResultsLocal 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.ConclusionThese findings indicate that VIP is involved in peripheral sensitization of knee joint afferents especially in response to normal joint movements. OA-induced sensitization of knee joint afferents was inhibited by local administration of VIP6–28, indicating that VIP is released into OA knee joints, potentially contributing to joint pain. As such, VIP6–28 may prove to be a beneficial agent for the treatment of arthritis pain.