Effect of selective sensory denervation on fracture-healing: an experimental study of rats.

Abstract

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