Degenerative lumbar disc disease: in vivo data support the rationale for the selection of appropriate animal models

Abstract

Since low-back pain is increasing in ageing populations, current research efforts are focused on obtaining a better understanding of the pathophysiology of intervertebral disc degeneration and on developing new therapeutic strategies. This requires adequate and clinically relevant models of the disease process. Ex vivo models can provide insights into isolated aspects of the degenerative/regenerative processes involved; although, ultimately, in vivo models are needed for preclinical translational studies. Such models have been developed in numerous animal species with significant variations in size and disc physiology and their number is considerable. Importantly, the choice of the model has to be tailored to the aim of the study. Given the number of available options, it is important to have a good understanding of the various models of disc degeneration and to be fully aware of their advantages and limitations. After comparing the anatomy and histology of intervertebral discs in animals and humans, the present study provides an overview of the different models of in vivo disc degeneration. It also provides a comprehensive guide with suggested criteria to select the most appropriate animal model in a question-driven manner.

Effect of voluntary running activity on mRNA expression of extracellular matrix genes in a mouse model of intervertebral disc degeneration

“…However, one model is unlikely to reflect the many potential mechanisms that may drive LBP or IDD in individuals. More studies are needed to determine if these results extend to other models (e.g., disc puncture or SM/J mice 27 , 49 , 50 ), are conserved across age, and are relevant to clinical settings.…”

A comprehensive tool box for large animal studies of intervertebral disc degeneration

“…for goats, pigs and sheep [5][6][7]150 and summarized by Fusellier et al 151 Furthermore, varying measurement methodologies (eg, application of axial load) makes comparison between the available studies difficult.…”

“…With the exception of dogs, IVD geometries have been reported for goats, pigs and sheep 5–7,150 and summarized by Fusellier et al 151 Furthermore, varying measurement methodologies (eg, application of axial load) makes comparison between the available studies difficult. Although basic geometries have been documented, anatomical details are still insufficient.…”

Correlation between magnetic resonance, X-ray imaging alterations and histological changes in an ovine model of age-related disc degeneration

“…Nevertheless, induction of IVD degeneration is invasive and can be time-consuming, as a considerable amount of time can be required to allow the onset and development of the degenerative process, depending on the induction modality used. For example, discectomy induces IVD degeneration after approximately 6 weeks (Sloan et al, 2020), while instability only induces this degeneration after at least 9 months (Fusellier et al, 2020). Additionally, IVD degeneration triggered by inductive methods can drastically influence the outcomes of the tested regenerative therapies, particularly in case of chemonucleolysis due to residual enzyme activity (Fusellier et al, 2020).…”