INTRODUCTION: The intervertebral disc has a poor propensity for regeneration. This may be due to the disc’s avascularity and limited nutrient supply. Small molecules must undergo trans-endplate transport from subchondral capillaries to metabolically active cells as far away as the central nucleus pulposus.¹ Increased biosynthesis in the disc in response to degeneration leads to increased metabolic activity and increase in demand for nutrients. If transport cannot meet demand, rapid depletion of nutrients and further degeneration can result.¹ Recently, low rate cyclic axial loading has been shown to increase transport of small molecules to and from a healthy disc via convective transport (bulk flow).² If transport can be augmented similarly in a degenerated disc, then an increase in nutrient supply could promote biosynthesis and regeneration. The purpose of this study was to determine if repeated cyclic loading could slow, arrest, or reverse the progression of disc degeneration in the rabbit lumbar spine.

METHODS: After IACUC approval, 56 New Zealand White rabbits were assigned to one of four treatment groups: (i) Control (no degeneration, n=19), (ii) 8 weeks degeneration (“8D”, n=14), (iii) 16 weeks degeneration (“16D”, n=10), or (iv) 8 weeks degeneration + 8 weeks therapy (“Therapy”, n=13). All animals underwent surgery to instrument the spine for cyclic loading of the L45 intervertebral disc.² All animals other than the controls underwent disc puncture to induce degeneration. Animals in the 8D and 16D groups were allowed to degenerate for 8 or 16 weeks, respectively. Animals in the Therapy group were first allowed to degenerate for 8 weeks, then underwent a cyclic loading regimen (0.5Hz, 3mm/s) for 2 hours a day, 5 days per week, for the next 8 weeks. T2-weighted MRI and histologic analysis were performed. Nucleus volume, T2 relaxation times, Pfirrmann, and modified Pfirrmann scales were used to assess disc health. Histology was evaluated using the ORS Spine Section grading system. Indicators of biosynthesis, inflammation, and matrix degradation were analyzed via gene expression. Data were analyzed via one-way ANOVA with Games Howell post-hoc analysis or Kruskal-Wallis Test with a Mann-Whitney post-hoc analysis.

RESULTS: Animals tolerated the surgery and daily loading well with no signs of distress or discomfort during loading. T2 relaxation times, nucleus volumes, Pfirrmann, modified Pfirrmann, ORS Spine Section histo score, and gene expression are summarized in Figure 1. Data demonstrate that punctured discs progressively degenerate from week 0 to week 16. In contrast, discs that were allowed to degenerate for 8 weeks and then underwent cyclic loading therapy for 8 weeks showed improvements that suggest disc regeneration.

DISCUSSION: We have demonstrated for the first time, the ability of a degenerated intervertebral disc to regenerate in response to a non-invasive, non-pharmacologic treatment regimen. As a result of the treatment, data from every metric indicate that disc heath, disc volume, and disc organization improved as a result of cyclic loading. Discs appeared to reverse the extent of degeneration and data suggest that discs regenerated back to an earlier stage of degeneration and in some animals resembled normal healthy discs.