Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur

Nathan J. Koewler, Katie T. Freeman, Ryan J. Buus, Monica B. Herrera, Juan M. Jimenez-Andrade, Joseph R. Ghilardi, Christopher M. Peters, Lucy J. Sullivan, Michael A. Kuskowski, Jack L. Lewis, Patrick W Mantyh

Research output: Contribution to journalArticle

69 Citations (Scopus)

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 ∼50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. Introduction: 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. Materials and 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 ∼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.

Original languageEnglish (US)
Pages (from-to)1732-1742
Number of pages11
JournalJournal of Bone and Mineral Research
Volume22
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Fracture Healing
Nerve Growth Factor
Inbred C57BL Mouse
Femur
Monoclonal Antibodies
Bone and Bones
Pain
Closed Fractures
Fracture Fixation
Adrenergic Fibers
Therapeutics
Periosteum
Antibodies
Low Back Pain
Osteoarthritis
Analgesics
Animal Models
Bone Marrow

Keywords

  • Bone
  • Bone histomorphometry
  • Neural factors
  • Rodent
  • Skeletal pain

ASJC Scopus subject areas

  • Surgery

Cite this

Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur. / Koewler, Nathan J.; Freeman, Katie T.; Buus, Ryan J.; Herrera, Monica B.; Jimenez-Andrade, Juan M.; Ghilardi, Joseph R.; Peters, Christopher M.; Sullivan, Lucy J.; Kuskowski, Michael A.; Lewis, Jack L.; Mantyh, Patrick W.

In: Journal of Bone and Mineral Research, Vol. 22, No. 11, 11.2007, p. 1732-1742.

Research output: Contribution to journalArticle

Koewler, NJ, Freeman, KT, Buus, RJ, Herrera, MB, Jimenez-Andrade, JM, Ghilardi, JR, Peters, CM, Sullivan, LJ, Kuskowski, MA, Lewis, JL & Mantyh, PW 2007, 'Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur', Journal of Bone and Mineral Research, vol. 22, no. 11, pp. 1732-1742. https://doi.org/10.1359/jbmr.070711
Koewler, Nathan J. ; Freeman, Katie T. ; Buus, Ryan J. ; Herrera, Monica B. ; Jimenez-Andrade, Juan M. ; Ghilardi, Joseph R. ; Peters, Christopher M. ; Sullivan, Lucy J. ; Kuskowski, Michael A. ; Lewis, Jack L. ; Mantyh, Patrick W. / Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur. In: Journal of Bone and Mineral Research. 2007 ; Vol. 22, No. 11. pp. 1732-1742.
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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 ∼50{\%}. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. Introduction: 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. Materials and 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 ∼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.",
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AU - Herrera, Monica B.

AU - Jimenez-Andrade, Juan M.

AU - Ghilardi, Joseph R.

AU - Peters, Christopher M.

AU - Sullivan, Lucy J.

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AU - Mantyh, Patrick W

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