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.
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.
Authors: Elizabeth Salisbury; Eric Rodenberg; Corinne Sonnet; John Hipp; Francis H Gannon; Tegy J Vadakkan; Mary E Dickinson; Elizabeth A Olmsted-Davis; Alan R Davis Journal: J Cell Biochem Date: 2011-10 Impact factor: 4.429
Authors: Elizabeth Salisbury; Corinne Sonnet; Michael Heggeness; Alan R Davis; Elizabeth Olmsted-Davis Journal: Crit Rev Eukaryot Gene Expr Date: 2010 Impact factor: 1.807
Authors: Peter Smitham; Lawrence Crossfield; Gillian Hughes; Allen Goodship; Gordon Blunn; Chantal Chenu Journal: J Orthop Res Date: 2014-04-07 Impact factor: 3.494
Authors: Martijn Hofman; Frederik Rabenschlag; Hagen Andruszkow; Julia Andruszkow; Diana Möckel; Twan Lammers; Aneta Kolejewska; Philipp Kobbe; Johannes Greven; Michel Paul Johan Teuben; Martijn Poeze; Frank Hildebrand Journal: Sci Rep Date: 2019-07-05 Impact factor: 4.379
Authors: Charles D Hwang; Chase A Pagani; Johanna H Nunez; Masnsen Cherief; Qizhi Qin; Mario Gomez-Salazar; Balram Kadaikal; Heeseog Kang; Ashish R Chowdary; Nicole Patel; Aaron W James; Benjamin Levi Journal: JCI Insight Date: 2022-07-22