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: Anna E Rapp, Jochen Kroner, Stephanie Baur, Fabian Schmid, Adrian Walmsley, Harald Mottl, Anita Ignatius
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 33 Issue 8 Pg. 1235-41 (Aug 2015) ISSN: 1554-527X [Electronic] United States
• PMID: 25876530 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Chemical References

• Nerve Growth Factors
• Receptor, trkA

Topics

• Analgesia
• Animals
• Fracture Healing (physiology)
• Fractures, Bone (physiopathology)
• Male
• Mice
• Nerve Growth Factors (antagonists & inhibitors, physiology)
• Pain (drug therapy, physiopathology)
• Receptor, trkA (antagonists & inhibitors, physiology)
• Signal Transduction (physiology)