title: The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  We demonstrate that anti-NGF antibody treatment attenuates OA pain behaviour despite permitting cartilage damage and synovitis. Indirect effects on subchondral bone remodelling may contribute to the analgesic effects of NGF blockade.
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
authors.forename: L N
authors.initials: LN
authors.lastname: Nwosu
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Burston
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Millns
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Sagar
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
authors.forename: P I
authors.initials: PI
authors.lastname: Mapp
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: P
authors.initials: P
authors.lastname: Meesawatsom
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bennett
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Medicine, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Walsh
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK. Electronic address: victoria.chapman@nottingham.ac.uk.
authors.forename: V
authors.initials: V
authors.lastname: Chapman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D020932:Nerve Growth Factor; D010003:Osteoarthritis; D010010:Osteoclasts; D010146:Pain; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020932:Nerve Growth Factor
keywords: Bone; Inflammation; Nerve growth factor; Osteoarthritis; Pain