| Long bones are richly innervated with a presence of sensory neurons in the periosteum, cortical bone, endosteum and bone marrow. Emerging evidence suggests that these nerves are involved in more than simple pain transmission. Nerve damage not only affects bone during development, but also contributes to bone loss following injury. As bone cells express receptors for several neurotransmitters, nerves may regulate bone metabolism through local release of neuropeptides.;The objective of this research was to elucidate the contribution of peripheral sensory nerves to bone adaptation. We used a chemical model of decreased nerve function, administering a naturally occurring compound, capsaicin, to neonatal mice. With the use of different imaging modalities and mechanical testing techniques, we assessed the effects of denervation on skeletal development. We next used a model of increased mechanical loading (tibial compression) to investigate how denervation alters the bone response to an anabolic stimulus. Finally, we measured changes in bone concentrations of neuropeptides CGRP and substance P in response to increased loading (tibial compression) and decreased loading (hindlimb unloading).;Capsaicin treatment resulted in shorter femurs possessing thinner trabeculae. Denervation also altered the bone response to increased mechanical loading, with capsaicin-treated mice exhibiting greater changes in bone mass and mineral apposition rates. Neuropeptide concentrations were also changed by the mechanical environment with an increase in CGRP following tibial compression. Our findings indicate an important role for sensory nerves in bone metabolism, and suggest a potential target for therapeutics aimed at bone diseases characterized by abnormal bone formation. |
