Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review

Intervertebral disc degeneration (IVDD), a widely recognized cause of lower back pain, is the leading cause of disability worldwide. A myriad of preclinical in vivo animal models of IVDD have been described in the literature. There is a need for critical evaluation of these models to better inform researchers and clinicians to optimize study design and ultimately, enhance experimental outcomes. The purpose of this study was to conduct an extensive systematic literature review to report the variability of animal species, IVDD induction method, and experimental timepoints and endpoints used in in vivo IVDD preclinical research. A systematic literature review of peer-reviewed manuscripts featured on PubMed and EMBASE databases was conducted in accordance with PRISMA guidelines. Studies were included if they reported an in vivo animal model of IVDD and included details of the species used, how disc degeneration was induced, and the experimental endpoints used for analysis. Two-hundred and fifty-nine (259) studies were reviewed. The most common species, IVDD induction method and experimental endpoint used was rodents(140/259, 54.05%), surgery (168/259, 64.86%) and histology (217/259, 83.78%), respectively. Experimental timepoint varied greatly between studies, ranging from 1 week (dog and rodent models), to >104 weeks in dog, horse, monkey, rabbit, and sheep models. The two most common timepoints used across all species were 4 weeks (49 manuscripts) and 12 weeks (44 manuscripts). A comprehensive discussion of the species, methods of IVDD induction and experimental endpoints is presented. There was great variability across all categories: animal species, method of IVDD induction, timepoints and experimental endpoints. While no animal model can replicate the human scenario, the most appropriate model should be selected in line with the study objectives to optimize experimental design, outcomes and improve comparisons between studies.