The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain

Xu, L.; Nwosu, Lilian Ngozi; Burston, J.J.; Millns, P.J.; Sagar, Devi Rani; Mapp, Paul I.; Meesawatsom, P.; Li, L.; Bennett, Andrew J.; Walsh, D.A.; Chapman, Victoria

Abstract

Objective: Nerve growth factor (NGF) has a pivotal role in peripheral hyperalgesia and inflammation; anti-NGF antibodies attenuate pain responses in inflammatory pain models, and in people with osteoarthritis (OA) or low back pain. The aim of this study was to characterise the peripheral mechanisms contributing to the analgesic effects of anti-NGF antibody treatment in an established model of joint pain, which mimics key clinical features of OA.
Design: Effects of preventative vs therapeutic treatment with an anti-NGF antibody (monoclonal antibody 911: muMab 911 (10 mg/kg, s.c.)) on pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWT)), cartilage damage, synovitis and numbers of subchondral osteoclasts were investigated in the monosodium iodoacetate (MIA) model. Potential direct effects of NGF on receptor activator of nuclear factor kappa-B ligand (RANKL) mediated osteoclastogenesis were investigated in cultured human osteoclasts.
Results: Intra-articular MIA injection resulted in significant pain behaviour, cartilage damage, synovitis and increased numbers of subchondral osteoclasts. Both preventative and therapeutic treatment with muMab 911 significantly prevented, or reversed, MIA-induced pain behaviour, but did not alter cartilage or synovial pathology quantified at the end of the treatment period. NGF did not facilitate RANKL driven osteoclast differentiation in vitro, but preventative or therapeutic muMab 911 reduced numbers of TRAP positive osteoclasts in the subchondral bone.
Conclusions: We demonstrate that anti-NGF antibody treatment attenuates OA pain behaviour despite permitting cartilage damage and synovitis. Indirect

Citation

Xu, L., Nwosu, L. N., Burston, J., Millns, P., Sagar, D. R., Mapp, P. I., Meesawatsom, P., Li, L., Bennett, A. J., Walsh, D., & Chapman, V. (2016). The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain. Osteoarthritis and Cartilage, 24(9), 1587-1595. https://doi.org/10.1016/j.joca.2016.05.015

• Journal Article Type: Article
• Acceptance Date: May 11, 2016
• Online Publication Date: May 18, 2016
• Publication Date: 2016-09
• Deposit Date: Sep 22, 2016
• Publicly Available Date: Sep 22, 2016
• Journal: Osteoarthritis and Cartilage
• Print ISSN: 1063-4584
• Electronic ISSN: 1522-9653
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 9
• Pages: 1587-1595
• DOI: https://doi.org/10.1016/j.joca.2016.05.015
• Keywords: Osteoarthritis; pain; bone; inflammation; nerve growth factor
• Public URL: https://nottingham-repository.worktribe.com/output/803473
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S1063458416301017
• Contract Date: Sep 22, 2016