title: Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.
abstract: A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis.
  
  
  BACKGROUND
  Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture.
  
  
  METHODS
  In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture.
  
  
  RESULTS
  Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing.
  
  
  CONCLUSIONS
  These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.
authors.affiliation: Neurosystems Center and Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Koewler
authors.forename: Katie T
authors.initials: KT
authors.lastname: Freeman
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Buus
authors.forename: Monica B
authors.initials: MB
authors.lastname: Herrera
authors.forename: Juan M
authors.initials: JM
authors.lastname: Jimenez-Andrade
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ghilardi
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Peters
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Sullivan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuskowski
authors.forename: Jack L
authors.initials: JL
authors.lastname: Lewis
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Mantyh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001696:Biomechanical Phenomena; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005269:Femur / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D010146:Pain / Q000188:drug therapy; D011859:Radiography; D014945:Wound Healing
chemical_list: D000911:Antibodies, Monoclonal; D020932:Nerve Growth Factor