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A micro-imaging study linking bone cancer pain with tumor growth and bone resorption in a rat model

Clinical & Experimental Metastasis volume 30, pages 225–236 (2013)Cite this article

Abstract

Bone metastases represent a frequent complication of advanced breast cancer. As tumor growth-induced bone remodeling progresses, episodes of severe pain and fractures of weight-bearing limbs increase. All of these skeletal-related events influence the patient’s quality of life and survival. In the present study, we sought to determine whether some of these pain-related behaviors could be directly correlated to tumor progression and bone remodeling. For this purpose, we used a rat model of bone cancer pain based on the implantation of mammary carcinoma cells in the medullary cavity of the femur. The bone content and tumor growth were monitored over time by magnetic resonance imaging (MRI) and micro X-ray computed tomography (μCT). The same animals were evaluated for changes in their reflexive withdrawal responses to mechanical stimuli (allodynia) and weight-bearing deficits. As assessed by MRI, we found a negative correlation between tumor volume and allodynia or postural deficits throughout the experiment. Using μCT, we found that the bone volume/total volume (BV/TV) ratios for trabecular and cortical bone correlated with both mechanical hypersensitivity and weight-bearing impairment. However, whereas trabecular BV/TV stabilized between days 7 and 10 post-tumor detection, the cortical bone loss reached its maximum at that time. Our imaging approach also allowed us to consistently detect the tumor before the onset of pain, paving the way for the preemptive identification of at-risk patients. Altogether, these results improve our understanding of the events leading to tumor-induced bone pain and could eventually help in the design of novel strategies for the management of bone diseases.

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Acknowledgments

This work is supported by grants from the Canadian Institutes of Health Research (CIHR) and the Cancer Research Society (CRS) awarded to P.S. It was also initiated by financial support from the Quebec Bio-Imaging Network and the network for Oral and Bone Health Research. L.D.-S. is the recipient of a Frederick Banting and Charles Best CIHR scholarship and is a trainee supported by the Canadian Arthritis Network. M.L. is the Canadian Research Chair in MRI. P.S. is a CIHR new investigator and director of the Sherbrooke’s Neuroscience Center. P.S. and M.L. are members of the FRSQ-funded Centre de recherche clinique Étienne-Lebel. We are also grateful to Nathalie Carrier at the Centre de Recherche Clinique Etienne-Lebel for her help with the statistical analysis.

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Affiliations

  1. Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada

    Louis Doré-Savard, Nicolas Beaudet & Philippe Sarret

  2. Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, J1H 5N4, Canada

    Luc Tremblay & Martin Lepage

  3. The Center for Bone and Periodontal Research, McGill University, 740 Dr Penfield Avenue, Rm 2200, Montreal, QC, H3A 1A4, Canada

    Yongjun Xiao

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  1. Louis Doré-Savard
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  2. Nicolas Beaudet
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  3. Luc Tremblay
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  6. Philippe Sarret
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Correspondence to Philippe Sarret.

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Doré-Savard, L., Beaudet, N., Tremblay, L. et al. A micro-imaging study linking bone cancer pain with tumor growth and bone resorption in a rat model. Clin Exp Metastasis 30, 225–236 (2013). https://doi.org/10.1007/s10585-012-9530-0

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  • DOI: https://doi.org/10.1007/s10585-012-9530-0

Keywords

  • Metastasis
  • MRI
  • Micro-CT
  • Dynamic weight bearing
  • Allodynia