Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model.

Yuan Tian,Tomohiro Onodera,Takuji Miyazaki,Dawei Liang,Norimasa Iwasaki,Koji Iwasaki,Ryosuke Hishimura,Mohamad Alaa Terkawi

doi:10.3390/ijms22052552

Abstract

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague–Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.

Highlights

Published: 4 March 2021Osteoarthritis (OA) is the most common type of arthritis that affects more than 300 million people globally and contributes to an economic burden on both patients and society [1,2]
The intra-articular injection of 100 μg of the nerve growth factor (NGF) antibody effectively relieved the pain in the OA model rat, as evidenced from improved weight-bearing performance (Figure 1a, saline, 1 μg, 10 μg, vs. 100 μg from week 3, Table S1), whereas 1 and 10 μg doses showed no pain-relieving effects
These results show that only 100 μg of NGF antibody could relieve the OA pain induced by MIA injection, as confirmed from the improvement in weight-bearing asymmetry but not allodynia

Summary

Introduction

Osteoarthritis (OA) is the most common type of arthritis that affects more than 300 million people globally and contributes to an economic burden on both patients and society [1,2]. According to the recent Osteoarthritis Research Society International white paper, OA has been considered a serious disease because of the lack of any efficient treatment [3]. The symptoms of OA include pain, joint stiffness, and disability that lead to a decline in patients’ quality of life, the loss of social labor, and an economic burden on the whole society. Pain is important in all clinical problems, as it is the cause of hospital visits for treatment and the main reason underlying poor quality of life and social labor loss [4]. More effective treatments that relieve OA pain are warranted

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