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Disc degeneration spreads: long-term behavioural, histologic and radiologic consequences of a single-level disc injury in active and sedentary mice

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Abstract

Study design

A multi-cohort, case–control rodent study.

Purpose

Investigate the long-term behavioural, histologic and radiologic consequences on the complete lumbar spine of L4/5 intervertebral disc (IVD) injury in mice and determine if increased physical activity mitigates the observed changes.

Methods

Cohorts of 2-month-old CD1 female mice underwent a single ventral puncture of the L4/5 IVD. 0.5-, 3- or 12-months after injury, general health (body weight and locomotor capacity), behavioural signs of axial discomfort (tail suspension, grip strength and FlexMaze assays) and radiating pain (von Frey and acetone tests) were assessed. Experimental groups with free access to an activity wheel in their home cages were including in the 12-month cohort. Lumbar disc status was determined using colorimetric staining and radiologic (X-ray and T2-MRI) analysis. Innervation was measured by immunoreactivity for PGP9.5 and calcitonin gene‐related peptide.

Results

No changes in general health or persistent signs of axial discomfort were observed up to one year post-injury. In contrast, signs of radiating pain developed in injured mice at 3 months post-injury, persisted up to 12 months and were reversed by long-term physical activity. At 12-months post-injury, degeneration was observed in non-injured lumbar discs. Secondary degenerating IVDs were similar to the injured discs by X-ray (narrowing) and T2-MRI (internal disc disruption) but did not show abnormal innervation. Increased physical activity had no impact on mechanically injured IVDs, but attenuated disc narrowing at other lumbar levels.

Conclusions

Mechanical injury of L4/5-IVDs induces delayed radiating pain and degeneration of adjacent discs; increased physical activity positively mitigated both.

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Available upon request.

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Acknowledgements

The authors thank the staff of McGill University’s Comparative Medicine and Animal Resources Centre, Alan Edwards Centre for Research on Pain, Douglas Brain Imaging Centre, and Centre for Bone and Periodontal Research for their support and expertise.

Funding

This work was supported by Canadian Institutes for Health Research Grants MOP-126046 and MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation.

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Authors and Affiliations

  1. Faculty of Dentistry, McGill University, Montreal, QC, Canada

    Magali Millecamps, Seunghwan Lee, Daniel Z. Foster & Laura S. Stone

  2. The Alan Edwards Centre for Research On Pain, McGill University, 740 Dr. Penfield Ave, suite 3200, Montreal, QC, H3A 0G1, Canada

    Magali Millecamps, Seunghwan Lee, Daniel Z. Foster & Laura S. Stone

  3. Departments of Anesthesiology, Pharmacology & Therapeutics, Neurology & Neurosurgery, Faculty of Medicine, McGill University, Montreal, QC, Canada

    Laura S. Stone

  4. Department of Anesthesiology, University of Minnesota, Minneapolis, USA

    Laura S. Stone

Authors
  1. Magali Millecamps
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  2. Seunghwan Lee
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  3. Daniel Z. Foster
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  4. Laura S. Stone
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Contributions

Data collection MM, PL, DF; Methodology, Material preparation, Project administration, Formal analysis: MM; Funding acquisition and Conceptualization by MM and LSS, Supervision and manuscript review & editing: LSS. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Magali Millecamps.

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Millecamps, M., Lee, S., Foster, D.Z. et al. Disc degeneration spreads: long-term behavioural, histologic and radiologic consequences of a single-level disc injury in active and sedentary mice. Eur Spine J 30, 2238–2246 (2021). https://doi.org/10.1007/s00586-021-06893-2

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  • DOI: https://doi.org/10.1007/s00586-021-06893-2

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