A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

Abstract

Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored.

Inhibiting tumor necrosis factor‐alpha at time of induced intervertebral disc injury limits long‐term pain and degeneration in a rat model

“…Specifically, annular puncture with chondroitinase ABC, complete Freund's adjuvant, and TNFα have all been used to induce moderate to severe IVD degeneration with significantly reduced IVD height, diminished proteoglycan content, loss of NP cells, and altered IVD biomechanics . While these studies contextualize the current model of painful IVD degeneration as a model of moderate to severe IVD degeneration, several comprehensive reviews of other animal models of IVD degeneration exist …”

FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration

“…Aging is a major risk factor for the initiation and progression of IDD (Miller et al, 1988), and given the increase in life expectancy worldwide (2015), it has become a priority to identify the causes and mechanisms of IDD to reveal new therapeutic targets and approaches. Previous studies have proven useful in demonstrating the importance of changes in the expression of genes encoding structural components of ECM and growth factor signaling mediators in the pathophysiology of IDD (reviewed in Vo et al, 2013; Daly, Ghosh, Jenkin, Oehme, & Goldschlager, 2016). However, the precise molecular events that lead to cell dysfunction and potentially initiate the degenerative cascade during aging remain unknown.…”

Cell therapy for the degenerating intervertebral disc

“…Among the 50 animal studies reviewed here, 28 studies used rabbits, 7 used rats, 5 used dogs, 6 pigs, and there were 1 goat, 2 sheep and 1 mouse study (Table 2). Sheep and goat have IVDs resembling those of humans in size and absence of notochordal cells,(91) but only 3 studies out of 50 used these models. Although the authors agree that a large animal model is critical given the risk of implant ejection and subsequent catastrophic injury, large animal studies are not consistently conducted before clinical trials.…”