Schuelert N, McDougall J J
Department of Physiology & Biophysics, University of Calgary, Calgary, Alberta, Canada.
Osteoarthritis Cartilage. 2006 Nov;14(11):1155-62. doi: 10.1016/j.joca.2006.04.016. Epub 2006 Jun 5.
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 VIP(6-28) could ameliorate joint mechanosensitivity in an animal model of osteoarthritis (OA).
OA was induced in male Wistar rats by intra-articular injection of 3mg 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 VIP(6-28).
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 VIP(6-28). In the OA group, application of VIP(6-28) 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.
These 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 VIP(6-28), indicating that VIP is released into OA knee joints, potentially contributing to joint pain. As such, VIP(6-28) may prove to be a beneficial agent for the treatment of arthritis pain.
本研究旨在探讨局部应用神经肽血管活性肠肽（VIP）是否能调节正常大鼠膝关节的关节伤害感受，以及VIP拮抗剂VIP（6 - 28）是否能改善骨关节炎（OA）动物模型中的关节机械敏感性。
通过关节内注射3mg单碘乙酸钠诱导雄性Wistar大鼠患骨关节炎，恢复期为14天。在经动脉近距离注射不同剂量的VIP和VIP（6 - 28）之前和之后，记录膝关节初级传入神经对关节正常旋转和有害性过度旋转的电生理反应。
向正常膝关节局部应用VIP会导致在膝关节正常旋转期间（高达180%，P<0.01；n = 17）和过度旋转期间（高达37%，P<0.01；n = 17）传入神经放电率显著提高。VIP诱导的敏化作用可被预先给予的VIP受体拮抗剂VIP（6 - 28）阻断。在OA组中，应用VIP（6 - 28）会导致在膝关节正常旋转期间（高达45%，P<0.05；n = 17）和过度旋转期间（高达34%，P<0.01；n = 15）传入神经放电率显著降低。
这些发现表明，VIP参与膝关节传入神经的外周敏化，尤其是对正常关节运动的反应。局部应用VIP（6 - 28）可抑制OA诱导的膝关节传入神经敏化，表明VIP释放到OA膝关节中，可能导致关节疼痛。因此，VIP（6 - 28）可能被证明是治疗关节炎疼痛的有益药物。
