Abstract
Background
Increased bone resorption is driven by augmented osteoclast activity in pathological states of the bone, including osteoporosis, fracture, and metastatic bone cancer. Pain is a frequent co‐morbidity in bone pathologies, and adequate pain management is necessary for symptomatic relief. Bone cancer is associated with severe skeletal pain and dysregulated bone remodeling, while increased osteoclast activity and bone pain are also observed in osteoporosis and during fracture repair. However, the effects of altered osteoclast activity and bone resorption on nociceptive processing of bone afferents remains unclear.
Methods
This study investigates whether physiologic osteoclasts and resulting changes in bone resorption can induce skeletal pain. We first assessed correlation between changes in bone microarchitecture (through µCT) and skeletal pain using standardised behavioural phenotyping assays in a mouse model of metastatic bone cancer. We then investigated whether increased activity of physiologic osteoclasts, and the associated bone resorption, is sufficient to induce skeletal pain using mouse models of localized and widespread bone resorption following administration of exogenous receptor activator of nuclear factor kappa B ligand (RANKL).
Results
Our data demonstrates that mice with bone cancer exhibit progressive pain behaviours that correlate with increased bone resorption at the tumour site. Systemic RANKL injections enhance osteoclast activity and associated bone resorption, without producing any changes in motor function or pain behaviours at both early and late timepoints.
Conclusion
These findings suggest activation of homeostatic osteoclasts alone is not sufficient to induce skeletal pain in mice.
from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2ZYcm1o
via IFTTT
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