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.
Bibliographical noteFunding Information:
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.
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.
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
- Animal model
- Degeneration spread
- Intervertebral disc injury
- Low back pain
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't