Animal Models of Disc Degeneration Using Puncture Injury: A 20 Year Perspective.

Background: Intervertebral disc (IVD) degeneration (IVDD) is a major cause of global disability. Three papers on puncture models of IVDD were published 20 years ago, transforming the application of preclinical animal models for pathophysiology and therapeutic screening studies. Methods: Narrative review describing historic and current usage of preclinical puncture models of IVDD, documenting their introduction to induce slow, progressive IVDD and evolution to include many injury types broadly called "puncture models." IVDD puncture models were reviewed for variability in species, needle gauge, puncture depth, IVD compartment, injectates, angle of puncture, motion of needle, and IVDD phenotype mimicked. Results: IVD puncture models gained prominence following seminal 2005 publications describing needle puncture to induce slow, progressive IVDD for screening therapies. Specific details of puncture methods were described for controlling injury severity to induce IVDD phenotypes, including slow progressive IVDD, severe IVDD, chronic IVDD, disc herniation, and Modic-like changes. Common measurements for characterizing IVDD were also described. Conclusions: Surgically induced IVD puncture injury animal models have evolved over decades to include many variations simulating distinct clinical phenotypes of IVDD. To facilitate cross-study comparisons, we recommend reporting a common set of injury features including needle gauge, puncture depth, injectates, puncture angle changes, needle motion, involvement of endplate and surrounding tissues, and phenotypes of IVDD mimicked. Surgically induced "outside-in" puncture injury models are valuable tools to test specific hypotheses and screening therapies.