Degeneration of the intervertebral discs, a process characterized by a cascade of cellular, biochemical, structural and functional changes, is strongly implicated as a cause of low back pain. Current treatment strategies for disc degeneration typically address the symptoms of low back pain without treating the underlying cause or restoring mechanical function. A more in-depth understanding of disc degeneration, as well as opportunities for therapeutic intervention, can be obtained by considering aspects of intervertebral disc development. Development of the intervertebral disc involves the coalescence of several different cell types through highly orchestrated and complex molecular interactions. The resulting structures must function synergistically in an environment that is subjected to continuous mechanical perturbation throughout the life of an individual. Early postnatal changes, including altered cellularity, vascular regression and altered extracellular matrix composition, might set the disc on a slow course towards symptomatic degeneration. In this Perspective, we review the pathogenesis and treatment of intervertebral disc degeneration in the context of disc development. Within this scope, we examine how model systems have advanced our understanding of embryonic morphogenesis and associated molecular signaling pathways, in addition to the postnatal changes to the cellular, nutritional and mechanical microenvironment. We also discuss the current status of biological therapeutic strategies that promote disc regeneration and repair, and how lessons from development might provide clues for their refinement.

Biomechanical study and literature review. To quantify the acute effect of needle diameter on the in vitro mechanical properties of cadaver lumbar discs in the rat and sheep. To review published in vivo animal studies and evaluate disc changes with respect to the relative needle size. There are many cases where a disc needle puncture or injection is applied to animal models: puncture injuries to induce degeneration, chemonucleolysis to induce degeneration, and delivery of disc therapies. It is not clear what role the size of the needle may have in the outcome. Mechanics were measured after sham phosphate buffered saline injection with a 27 G or 33 G needle in the rat and with a 27 G needle in the sheep. A literature review was performed to evaluate studies in which animal discs were treated with a needle puncture or a sham injection. For each study, the ratio of the needle diameter to disc height (needle:height) was calculated. When the rat was injected with a 27 G needle (52% of disc height), the compression, tension, and neutral zone stiffnesses were 20% to 60% below preinjected values and the neutral zone length was 130% higher; when injected with a 33 G needle (26% of disc height), the only affected property was the neutral zone length, which was only 20% greater. When the sheep was injected with a 27 G needle (10% of disc height), none of the axial properties were different from intact, the torsion stiffness was not different, and the torque range was 15% smaller. Twenty-three in vivo studies in the rat, rabbit, dog, or sheep were reviewed. The disc changes depended on the ratio of needle diameter to disc height as follows: significant changes were not observed for needle:height less than 40%, although between 25% and 40% results were variable and some minor nonsignificant effects were observed, disc changes were universal for needle:height over 40%. A needle puncture may directly alter mechanical properties via nucleus pulposus depressurization and/or anulus fibrosus damage, depending on the relative needle size. As more basic science research is aimed at treating disc degeneration via injection of therapeutic factors, these findings provide guidance in design of animal studies. Such studies should consider the relative needle size and include sham control groups to account for the potential effects of the needle injection.

Study Design. T_1ρ relaxation was quantified and correlated with intervertebral disc degeneration and proteoglycan content in cadaveric human lumbar spine tissue. Objective. To show the use of T_1ρ-weighted magnetic resonance imaging (MRI) for the assessment of degeneration and proteoglycan content in the human intervertebral disc. Summary of Background Data. Loss of proteoglycan in the nucleus pulposus occurs during early degeneration. Conventional MRI techniques cannot detect these early changes in the extracellular matrix content of the disc. T_1ρ MRI is sensitive to changes in proteoglycan content of articular cartilage and may, therefore, be sensitive to proteoglycan content in the intervertebral disc. Methods. Intact human cadaveric lumbar spines were imaged on a clinical MR scanner. Average T_1ρ in the nucleus pulposus was calculated from quantitative T_1ρ maps. After MRI, the spines were dissected, and proteoglycan content of the nucleus pulposus was measured. Finally, the stage of degeneration was graded using conventional T₂ images. Results. T_1ρ decreased linearly with increasing degeneration (r = −0.76, P < 0.01) and age (r = −0.76, P < 0.01). Biochemical analysis revealed a strong linear correlation between T_1ρ and sulfated-glycosaminoglycan content. T_1ρ was moderately correlated with water content. Conclusions. Results from this study suggest that T_1ρ may provide a tool for the diagnosis of early degenerative changes in the disc. T_1ρ-weighted MRI is a noninvasive technique that may provide higher dynamic range than T₂ and does not require a high static field or exogenous contrast agents.