Merck
  • Home
  • Search Results
  • Analgesia via blockade of NGF/TrkA signaling does not influence fracture healing in mice.

Analgesia via blockade of NGF/TrkA signaling does not influence fracture healing in mice.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2015-04-17)
Anna E Rapp, Jochen Kroner, Stephanie Baur, Fabian Schmid, Adrian Walmsley, Harald Mottl, Anita Ignatius
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Citric acid trisodium salt, anhydrous, ≥98% (GC)
Sigma-Aldrich
Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
Sigma-Aldrich
Citrate Concentrated Solution, BioUltra, for molecular biology, 1 M in H2O
Sigma-Aldrich
Formaldehyde-12C solution, 20% in H2O, 99.9 atom % 12C
Sigma-Aldrich
Formaldehyde solution, meets analytical specification of USP, ≥34.5 wt. %
Sigma-Aldrich
Formaldehyde solution, for molecular biology, BioReagent, ≥36.0% in H2O (T)
Sigma-Aldrich
Formaldehyde solution, for molecular biology, 36.5-38% in H2O
Sigma-Aldrich
Citrate Concentrated Solution, BioReagent, suitable for coagulation assays, 4 % (w/v)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Phenylacetic acid, suitable for plant cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Phenylacetic acid, ≥99%, FCC, FG
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Phenylacetic acid, 99%