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

Int J Mol Sci. 2021 Mar 4;22(5):2552. 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.

Keywords: intra-articular injection; nerve growth factor (NGF); osteoarthritis; pain.

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / physiopathology
  • Arthritis, Experimental / therapy*
  • Cartilage, Articular / pathology
  • Dose-Response Relationship, Immunologic
  • Hyperalgesia / physiopathology
  • Hyperalgesia / therapy
  • Injections, Intra-Articular
  • Iodoacetic Acid / toxicity
  • Male
  • Nerve Growth Factor / antagonists & inhibitors*
  • Nerve Growth Factor / immunology
  • Osteoarthritis / pathology
  • Osteoarthritis / physiopathology
  • Osteoarthritis / therapy*
  • Pain Management / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Weight-Bearing / physiology

Substances

  • Antibodies, Monoclonal, Humanized
  • Nerve Growth Factor
  • tanezumab
  • Iodoacetic Acid