Animal Models of Intervertebral Disc Degeneration

In Brief Study Design. A literature review of intervertebral disc degeneration animal models. Objectives. Focus is placed on those models that suggest degeneration mechanisms relevant to human. Summary of Background Data. Medical knowledge from observational epidemiology and intervention studies suggest many etiologic causal factors in humans. Animal models can provide basic science data that support biologic plausibility as well as temporality, specificity, and dose-response relationships. Methods. Studies are classified as either experimentally induced or spontaneous, where experimentally induced models are subdivided as mechanical (alteration of the magnitude or distribution of forces on the normal joint) or structural (injury or chemical alteration). Spontaneous models include those animals that naturally develop degenerative disc disease. Results. Mechanobiologic relationships are apparent as stress redistribution secondary to nuclear depressurization (by injury or chemical means) can cause cellular metaplasia, tissue remodeling, and pro-inflammatory factor production. Moderate perturbations can be compensated for by cell proliferation and matrix synthesis, whereas severe perturbations cause architectural changes consistent with human disc degeneration. Conclusions. These models suggest that two stages of architectural remodeling exist in humans: early adaptation to gravity loading, followed by healing meant to reestablish biomechanical stability that is slowed by tissue avascularity. Current animal models are limited by an incomplete set of initiators and outcomes that are only indirectly related to important clinical factors (pain and disability). This literature review of animal models of intervertebral disc degeneration demonstrates biomechanical biologic synergy between anulus fibrosus, cartilage endplate, nucleus pulposus. Nuclear depressurization invariably leads to stress redistribution remodeling that causes morphologic changes characteristic of human disc degeneration. Despite their limitations, animal models suggest that disc degeneration in humans can be characterized by sluggish adaptation to gravity loading in the early stages, followed by obstructed healing due to tissue avascularity. Future studies should focus on improving the correspondence of the initiating factors outcomes between animal models human observational epidemiology intervention studies.