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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2017

Open Access 01-12-2017 | Research article

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

Authors: Masayuki Miyagi, Tetsuhiro Ishikawa, Hiroto Kamoda, Miyako Suzuki, Gen Inoue, Yoshihiro Sakuma, Yasuhiro Oikawa, Sumihisa Orita, Kentaro Uchida, Kazuhisa Takahashi, Masashi Takaso, Seiji Ohtori

Published in: BMC Musculoskeletal Disorders | Issue 1/2017

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Abstract

Background

Nerve 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.

Method

Six-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.

Results

On 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).

Conclusions

MIA 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.
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Metadata
Title
Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice
Authors
Masayuki Miyagi
Tetsuhiro Ishikawa
Hiroto Kamoda
Miyako Suzuki
Gen Inoue
Yoshihiro Sakuma
Yasuhiro Oikawa
Sumihisa Orita
Kentaro Uchida
Kazuhisa Takahashi
Masashi Takaso
Seiji Ohtori
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2017
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-017-1792-x

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