Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice

BMC Musculoskeletal Disorders

Research Article

Miyako Suzuki¹  Hiroto Kamoda¹  Yasuhiro Oikawa¹  Sumihisa Orita¹  Tetsuhiro Ishikawa¹  Kazuhisa Takahashi¹  Yoshihiro Sakuma¹  Seiji Ohtori¹  Kentaro Uchida²  Gen Inoue²  Masashi Takaso²  Masayuki Miyagi² 

[1] Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan;Department of Orthopaedic Surgery, Kitasato University, School of Medicine, 1-15-1, Kitasato, Minami-ku, 252-0374, Sagamihara city, Kanagawa, Japan;

关键词: Nerve growth factor;    Anti-nerve growth factor therapy;    Knee osteoarthritis;    Monoiodoacetate;    CatWalk;    Calcitonin gene-related peptide;    Dorsal root ganglia;   

DOI  :  10.1186/s12891-017-1792-x

 received in 2017-02-03, accepted in 2017-10-30,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice.MethodSix-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4–L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted.ResultsOn gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p < 0.05).ConclusionsMIA injection into the knee joint induced gait impairment and the up-regulation of CGRP in DRG neurons in a knee OA pain model in mice. Intraperitoneal injection of anti-NGF antibody suppressed this impairment of gait and up-regulation of CGRP in DRG neurons. These finding suggest that anti-NGF therapy might be valuable in the treatment of OA pain in the knee.

【 授权许可】

CC BY   
© The Author(s). 2017