The Journal of Bone and Joint Surgery (American). 2009;91:2886-2895.
doi:10.2106/JBJS.H.01878
© 2009 The Journal of Bone and Joint Surgery, Inc.
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Effect of Selective Sensory Denervation on Fracture-Healing

An Experimental Study of Rats

Peter J. Apel, MD1, Daniel Crane, BS1, Casey N. Northam, BS1, Michael Callahan, PhD1, Thomas L. Smith, PhD1 and Robert D. Teasdall, MD1

1 Department of Orthopaedic Surgery, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157. E-mail address for P.J. Apel: papel{at}wfubmc.edu

Investigation performed at the Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Orthopaedic Trauma Association and the Department of Surgery, Wake Forest University School of Medicine. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Background: Interactions between the peripheral nervous system and the healing skeleton are poorly understood. Various clinical observations suggest that the nervous system interacts with and promotes fracture-healing. The purpose of this study was to examine the effect of selective sensory denervation on fracture-healing.

Methods: Fifty-one Sprague-Dawley rats underwent unilateral placement of an intramedullary rod followed by creation of a standardized femoral fracture. One group of these rats underwent sensory denervation by means of a localized capsaicin injection, and the other did not. Subgroups were allocated for analysis of mRNA expression of collagen I and II and osteocalcin at three, seven, and fourteen days after the fracture. Additionally, histological examination was performed at four weeks; micro-computed tomography, at five weeks; and biomechanical testing, at six weeks.

Results: The sensory-denervated group had significantly less collagen-I upregulation than the sensory-intact group at three days after the fracture (difference in means, forty-four-fold [95% confidence interval = 22.7 to 65.5-fold]; p < 0.001) and significantly less collagen-II upregulation at seven days after the fracture (difference in means, ninefold [95% confidence interval = 4.3 to 13.8-fold]; p < 0.001). In the sensory-denervated group, the fracture callus had a significantly larger cross-sectional area (difference in means, 15.6 mm2 [95% confidence interval = 0.78 to 30.5 mm2]; p = 0.043) and was less dense. Biomechanical testing revealed that sensory denervation significantly decreased the load to failure (difference in means, 28.7 N [95% confidence interval = 1.2 to 56.2 N]; p = 0.022).

Conclusions: Sensory denervation negatively affects fracture-healing. These results offer insight into the nerve-bone interaction following injury.

Clinical Relevance: These results are relevant to clinicians and researchers who are seeking to improve fracture-healing in patients with associated peripheral nerve injury or peripheral neuropathy.


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