title: Analgesia via blockade of NGF/TrkA signaling does not influence fracture healing in mice.
abstract: Abatement of fracture-related pain is important in patient welfare. However, the frequently used non-steroidal anti-inflammatory drugs are considered to impair fracture healing through blockade of cyclooxygenase-2. An alternative for fracture-related pain treatment may be blockade of nerve growth factor (NGF)/neurotrophic tyrosine kinase receptor type 1 (TrkA) signaling. Because the effect of blocking this signal-pathway on bone healing has not been extensively investigated, we addressed this issue by applying neutralizing antibodies that target NGF and TrkA, respectively, in a mouse fracture model. Mice with a knock-in for human TrkA underwent femur osteotomy and were randomly allocated to phosphate-buffered-saline, anti-NGF-antibody, or anti-TrkA-antibody treatment. The analgesic effect of the antibodies was determined from the activity and the ground reaction force of the operated limb. The effect of antibody administration on fracture healing was assessed by histomorphometry, micro-computed tomography, and biomechanics. NGF/TrkA-signaling blockade had no negative effect on fracture healing as callus formation and maturation were not altered. Mice treated with anti-TrkA antibody displayed significantly greater activity on post-operative day 2 compared to PBS treatment indicating effective analgesia. Our data indicate, that blockade of NGF/TrkA signaling via specific neutralizing antibodies for pain reduction during fracture healing does not influence fracture healing.
authors: Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research Ulm (zmfu), University of Ulm, Ulm, Germany.
authors: Anna E
authors: AE
authors: Rapp
authors: Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research Ulm (zmfu), University of Ulm, Ulm, Germany.
authors: Jochen
authors: J
authors: Kroner
authors: Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research Ulm (zmfu), University of Ulm, Ulm, Germany.
authors: Stephanie
authors: S
authors: Baur
authors: Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research Ulm (zmfu), University of Ulm, Ulm, Germany.
authors: Fabian
authors: F
authors: Schmid
authors: Glenmark Pharmaceuticals Limited, La Chaux-de-Fonds, Switzerland.
authors: Adrian
authors: A
authors: Walmsley
authors: Glenmark Pharmaceuticals Limited, La Chaux-de-Fonds, Switzerland.
authors: Harald
authors: H
authors: Mottl
authors: Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research Ulm (zmfu), University of Ulm, Ulm, Germany.
authors: Anita
authors: A
authors: Ignatius
mesh_terms: D000698:Analgesia; D000818:Animals; D017102:Fracture Healing / Q000502:physiology*; D050723:Fractures, Bone / Q000503:physiopathology; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D009414:Nerve Growth Factors; D020917:Receptor, trkA
keywords: NGF; Tanezumab; analgesia; fracture healing; nerve growth factor receptor