Animal models of intervertebral disc degeneration - Lessons learned

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).