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 mm 2 [95% confidence interval= 0.78 to 30.5 mm 2]; 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.