Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan.
Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo 060-0808, Japan.
Int J Mol Sci. 2021 Mar 4;22(5):2552. doi: 10.3390/ijms22052552.
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.
全身注射神经生长因子 (NGF) 抗体已被证明对缓解骨关节炎 (OA) 疼痛具有显著相关性，但其不良反应仍然是患者关注的安全问题。局部低剂量注射被认为可以最大程度地减少不良反应。在这项研究中，通过向 8 周龄雄性 Sprague-Dawley (SD) 大鼠关节注射单碘乙酸 (MIA) 2 周来诱导 OA，然后评估每周注射低剂量 (1、10 和 100 µg) NGF 抗体或生理盐水 (对照) 的效果。进行行为测试，在第 6 周末，所有大鼠被处死，收集其膝关节进行宏观和组织学评估。结果表明，100 µg NGF 抗体注射减轻了 OA 大鼠的疼痛，这从改善的负重表现中得到证实，但没有痛觉过敏。相比之下，不同组大鼠的宏观和组织学评分之间没有观察到显著差异，表明关节内治疗不会加重 OA 进展。这些结果表明，局部给药产生了低有效 NGF 抗体剂量，可作为治疗 OA 患者的全身注射的替代方法。
