Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.
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.
Koewler
Nathan J
NJ
Neurosystems Center and Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
Freeman
Katie T
KT
Buus
Ryan J
RJ
Herrera
Monica B
MB
Jimenez-Andrade
Juan M
JM
Ghilardi
Joseph R
JR
Peters
Christopher M
CM
Sullivan
Lucy J
LJ
Kuskowski
Michael A
MA
Lewis
Jack L
JL
Mantyh
Patrick W
PW
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
D000911:Antibodies, Monoclonal; D020932:Nerve Growth Factor