Abstract
BackgroundThe rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models.AimsThe purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model.Materials and MethodsThe scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors.ResultsThe final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus.DiscussionOverall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field.ConclusionThis study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.
Highlights
The intervertebral discs of the spine are the composite, avascular structures which reside between bony vertebral bodies and are responsible for bearing often high magnitude loads derived from complex spinal motion during activities of daily living.[1,2] The intervertebral disc is composed of the highly hydrated, proteoglycan-rich nucleus pulposus (NP), surrounded by the annulus fibrosus (AF), which is composed of lamellae of primarily type I collagen fibers with alternating ±30 orientation to the transverse plane.[3]
We have proposed a new standardized histopathology scoring system to assess disc degeneration and regeneration in the rabbit lumbar spine, based on previous literature and current practices by research groups in the field
As a majority of studies in the rabbit model that perform histology scoring have utilized the grading scheme proposed in 2005 by Masuda et al,[11,19] this scoring system was utilized as the basis of the proposed scoring system
Summary
The intervertebral discs of the spine are the composite, avascular structures which reside between bony vertebral bodies and are responsible for bearing often high magnitude loads derived from complex spinal motion during activities of daily living.[1,2] The intervertebral disc is composed of the highly hydrated, proteoglycan-rich nucleus pulposus (NP), surrounded by the annulus fibrosus (AF), which is composed of lamellae of primarily type I collagen fibers with alternating ±30 orientation to the transverse plane.[3]. Intervertebral disc degeneration is associated with a variety of structural, compositional, and mechanical perturbations to all of the disc substructures.[6] Degeneration of the intervertebral discs is considered to be a major contributor to back pain, which has become a primary cause of disability globally.[7,8] Studying the etiology and progression of disc degeneration in humans can be difficult, costly, and time consuming, and as such, animal models are commonly used to study the progression of this disease or to evaluate the efficacy of new therapeutic interventions to affect disc regeneration.[9,10] The rabbit lumbar spine is a common preclinical model to study disc degeneration and to evaluate therapeutic interventions.[11,12] The rabbit model has the advantage of cost-effectiveness compared to larger animal models (ie, canine, sheep, goats), while possessing comparable anatomy to humans because of the presence of facet joints, paravertebral muscles and ligaments compared to the commonly utilized rodent tail models. We performed three studies: (a) a literature review of published papers utilizing the rabbit model, (b) a survey of spine researchers, and (c) validation of the new scoring system
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