Nerve growth factor monoclonal antibody Tanezumab alleviates Kashin-Beck Disease Rat pain by impacting DRG signal transduction

Abstract

Abstract Objective This study aimed to determine NGF monoclonal antibody’s effectiveness for KBD. Method After the establishment of KBD models in SD rats, the rats were injected with the NGF monoclonal antibody Tanezumab(Tnz) at doses of 2.5 and 5.0 mg/kg every week subcutaneously for 4 weeks. Paw withdraw mechanical threshold(PWT) was measured with Von Frey hairs, and Thermal paw withdraw latency(PWL) was valued by radiant heat. Serum TNF-α and IL-1β were also tested by ELISA during the whole process. After 4 weeks of treatment, rats were sacrificed to gather the dorsal root ganglion, in which protein levels of NGF/Trka signaling were detected by immunofluorescence and western blotting. Result The KBD model was established successfully, during which the PWT and PWL of KBD inducing rats decreased gradually, and TNF-α and IL-1β increased significantly. After 4 weeks of Tnz treatment, both the PWL and PWT of KBD rats significantly increased, and TNF-α and IL-1β also decreased, on which 5.0mg/kg of TNZ was better than 2.5mg/kg. Western blotting told that Tnz could reduce the level of the Trka pathway in DRG of KBD rats, and 5.0mg/kg TNZ could induce further reduction than 2.5mg/kg. Immunofluorescence showed that the levels of BDNF and CGRP in the DRG of KBD rats increased, and 5.0mg/kg of Tnz could significantly rescue them. Conclusion Tnz can alleviate the pain of KBD rats by inhibiting activated Trka levels, and 5.0mg/kg is more effective than 2.5mg/kg. TNZ is a potential analgesic for KBD, but clinical trials are essential before clinic application.