Needle puncture injury causes acute and long-term mechanical deficiency in a mouse model of intervertebral disc degeneration

Abstract

Low back pain is a significant socioeconomic burden and intervertebral disc degeneration has been implicated as a cause. A reliable animal model of disc degeneration is necessary to evaluate therapeutics, and functional metrics are essential to quantify their benefit. To this end, needle puncture injuries were created in the caudal intervertebral discs of mice to induce disc degeneration. Compression, torsion, and creep mechanics were assessed both immediately and after eight weeks to distinguish between the effects of injury and the subsequent reparative or degenerative response. Two needle sizes (29 and 26 gauge) were used to determine injury sizedependence. Compressive stiffness (62%), torsional stiffness (60%), and early damping stiffness (84%) decreased immediately after injury with the large needle (26G). These mechanical properties did not change over time despite structural and compositional changes. At 8 weeks following large needle injury, disc height decreased (37%), nucleus pulposus (NP) glycosaminoglycan content decreased (41%), and NP collagen content increased (45%). The small needle size had no significant effect on mechanics and did not initiate degenerative changes in structure and composition. Thus, the injection of therapeutics into the NP with a minimal needle size may limit damage due to the needle insertion. These findings, along with the wide commercial availability of mouse-specific biological probes, indicate that the mouse caudal disc model can be a powerful tool for investigating disc degeneration and therapy.

Does a small size needle puncture cause intervertebral disc changes?

“…Opposing, in mice, the caudal disc puncture with a small gauge needle (29-gauge) did not initiate degenerative changes in disc structure and composition 4 . Since our group and others, have regularly used the 30-gauge needle for intradiscal injection of innocuous or potential therapeutic compounds, our aim was to investigate if this procedure could trigger observable changes on intervertebral disc.…”

“…Among others, the degenerative process induced by needle puncture has gained popularity because it is uncomplicated, reproducible, and cost-effective, and requires a short time to produce the disc degeneration [2][3][4] . While human disc degeneration is a complex and multifactorial process that occurs over decades, the limited anular injury induced by needle puncture is a potential initiator of disc degeneration 2,3 .…”

“…While human disc degeneration is a complex and multifactorial process that occurs over decades, the limited anular injury induced by needle puncture is a potential initiator of disc degeneration 2,3 . Usually, needles with 18-22 gauge can produce morphologically and biochemically altered features similar to many of those found in human degenerative disc disease [3][4][5] . Conversely, small size needles, equal or superior to 29-gauge, are necessary to perform intradiscal injection in experimental conditions, which represents a controversial procedure in experimental practice, but also in clinical situation [6][7][8] .…”

Intervertebral Disc Degeneration and Low Back Pain: Molecular Mechanisms and Stem Cell Therapy

“…(200)(201)(202)(203) Increased production of cytokines, particularly TGF-b favors these transformations. (203)(204)(205) The NP contains MSC that are similar to the MSC recovered from bone marrow (206), and studies in animal models of DD have shown that MSC injected in the NP area not only survive for months but also proliferate in canine (207,208), porcine (209), and rabbit models (210). Moreover, the transplanted MSC induced production of extracellular matrix proteins, including aggrecan and other proteoglycans, and types I and II collagens.…”

“…Moreover, the transplanted MSC induced production of extracellular matrix proteins, including aggrecan and other proteoglycans, and types I and II collagens. (207,209,210) A major limitation of using stem cells as a therapy for IDD is an appropriate delivery method that will not cause further injury to the IVD. The most direct route is an injection into the affected IVD, ensuring a localized therapeutic effect.…”