Combined flexion and compression negatively impact the mechanical integrity of the annulus fibrosus.

PURPOSE: To observe the effect of static flexion, in combination with compression, on the intralamellar and interlamellar matrix properties of the annulus fibrosus. METHODS: C3/C4 cervical functional spinal units of porcine specimens were selected. Following preloading, all specimens were loaded under 1200 N axial compression in either a neutral or static end range flexion posture (15º) for 2 h. Following loading, six annulus samples were dissected from each disc: four single-layer and two multi-layer samples. The multi-layer samples underwent peel tests to quantify the mechanical properties of the interlamellar matrix while the single-layer samples underwent tensile tests to quantify the mechanical properties of the intralamellar matrix. Statistical comparisons between properties were performed to determine differences between postural condition, extraction location, and extraction depth. RESULTS: Flexion elicited a decrease in lamellar adhesive strength (p = 0.045) and in single-layer failure strain (p = 0.03) when compared to a neutral posture. Flexion also had extraction depth-specific effects namely increased intralamellar matrix stiffness in the inner annulus when compared to neutral (p = 0019). Flexion also resulted in a significant decrease in toe region strain for the inner region of the annulus (p = 0.035). The inner region of the annulus was shown to have a significant increase in stress at 30% strain when compared to the outer region after flexion (p = 0.041). CONCLUSION: The current findings suggest that the mechanical properties of the interlamellar and intralamellar matrices are sensitive to flexion, creating an environment that promotes an increased potential for damage to occur.

TAK-242 treatment and its effect on mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

PURPOSE: Intervertebral disc (IVD) degeneration is accompanied by mechanical and gene expression changes to IVDs. SPARC-null mice display accelerated IVD degeneration, and treatment with (toll-like receptor 4 (TLR4) inhibitor) TAK-242 decreases proinflammatory cytokines and pain. This study examined if chronic TAK-242 treatment impacts mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice. METHODS: Male and female SPARC-null and WT mice aged 7-9 months were given intraperitoneal injections with TAK-242 or an equivalent saline vehicle for 8 weeks (3x/per week, M-W-F). L2-L5 spinal segments were tested in cyclic axial tension and compression. Gene expression analysis (RT-qPCR) was performed on male IVD tissues using Qiagen RT2 PCR arrays. RESULTS: SPARC-null mice had decreased NZ length (p = 0.001) and increased NZ stiffness (p < 0.001) compared to WT mice. NZ length was not impacted by TAK-242 treatment (p = 0.967) despite increased hysteresis energy (p = 0.024). Tensile stiffness was greater in SPARC-null mice (p = 0.018), and compressive (p < 0.001) stiffness was reduced from TAK-242 treatment in WT but not SPARC-null mice (p = 0.391). Gene expression analysis found upregulation of 13 ECM and 5 inflammatory genes in SPARC-null mice, and downregulation of 2 inflammatory genes after TAK-242 treatment. CONCLUSIONS: TAK-242 had limited impacts on SPARC-null mechanical properties and did not attenuate NZ mechanical changes associated with IVD degeneration. Expression analysis revealed an increase in ECM and inflammatory gene expression in SPARCnull mice with a reduction in inflammatory expression due to TAK-242 treatment. This study provides insight into the role of TLR4 in SPARC-null mediated IVD degeneration.

Glycerol induced paraspinal muscle degeneration leads to hyper-kyphotic spinal deformity in wild-type mice.

Degenerative spinal disorders, including kyphotic deformity, are associated with a range of degenerative characteristics of the paraspinal musculature. It has therefore been hypothesized that paraspinal muscular dysfunction is a causative factor for degenerative spinal deformity; however, experimental studies demonstrating causative relationships are lacking. Male and female mice received either glycerol or saline injections bilaterally along the length of the paraspinal muscles at four timepoints, each separated by 2 weeks. Immediately after sacrifice, micro-CT was performed to measure spinal deformity; paraspinal muscle biopsies were taken to measure active, passive and structural properties; and lumbar spines were fixed for analysis of intervertebral disc (IVD) degeneration. Glycerol-injected mice demonstrated clear signs of paraspinal muscle degeneration and dysfunction: significantly (p < 0.01) greater collagen content, lower density, lower absolute active force, greater passive stiffness compared to saline-injected mice. Further, glycerol-injected mice exhibited spinal deformity: significantly (p < 0.01) greater kyphotic angle than saline-injected mice. Glycerol-injected mice also demonstrated a significantly (p < 0.01) greater IVD degenerative score (although mild) at the upper-most lumbar level compared to saline-injected mice. These findings provide direct evidence that combined morphological (fibrosis) and functional (actively weaker and passively stiffer) alterations to the paraspinal muscles can lead to negative changes and deformity within the thoracolumbar spine.

Delamination of the Annulus Fibrosus of the Intervertebral Disc: Using a Bovine Tail Model to Examine Effect of Separation Rate.

The intervertebral disc (IVD) is a complex structure, and recent evidence suggests that separations or delamination between layers of the annulus may contribute to degeneration development, a common cause of low back pain The purpose of the present experiment was to quantify the mechanical response of the layer-adjoining interlamellar matrix at different rates of separation. Understanding the rate-dependency of the interlamellar matrix, or the adhesion between adjacent layers of the disc, is important as the spine experiences various loading velocities during activities of daily living. Twelve discs were dissected from four bovine tails (three extracts per tail). Two multi-layered annulus samples were collected from each IVD (total = 24, mean bond width = 3.82 ± 0.96 mm) and randomly assigned to a 180° peel test at one of three delamination rates; 0.05 mm/s, 0.5 mm/s, or 5 mm/s. Annulus extracts were found to have similar maximal adhesion strengths (p = 0.39) and stiffness (p = 0.97) across all rate conditions. However, a significant difference in lamellar adhesion strength variability was observed between the 5 mm/s condition (0.96 N/mm ± 0.31) when compared to the 0.5 mm/s (0.50 N/mm ± 0.19) and 0.05 mm/s (0.37 N/mm ± 0.13) conditions (p < 0.05). Increased variability may be indicative of non-uniform strength due to inconsistent adhesion throughout the interlamellar matrix, which is exacerbated by increased rates of loading. The observed non-uniform strength could possibly lead to a scenario more favourable to the development of microtrauma, and eventual delamination.

The effect of head and gaze orientation on spine kinematics during forward flexion.

Compound, or awkward, spine postures have been suggested as a biomechanical risk factor for low back injury. This experiment investigates the influence of head (i.e. head-on-torso) and gaze (i.e. eye-in-head) orientation on three-dimensional (3D) neck and spine range of motion (ROM) during forward flexion movements. To emulate previous experimental protocols and replicate real-world scenarios, a sample of ten young, healthy males (mean ± standard deviation: age: 20.8 ± 1.03 years, height: 180.2 ± 7.36 cm, and mass: 81.9 ± 6.47 kg) completed forward flexion movements with a constrained and unconstrained pelvis, respectively. Surface kinematics were gathered from the head and spine (C7-S1). Movements were completed under a baseline condition as well as upward, downward, leftward, and rightward head and gaze orientations. For each condition, mean neck angle and inter-segmental spine (C7T1 through L5S1) ROM were evaluated. The results demonstrate that directed head and gaze orientations can influence the ROM of specific spine regions during a forward flexion task. With leftward and rightward directed head and gaze orientations, the neck became increasingly twisted and superior thoracic segments (i.e. C7T1-T2T3) were significantly more twisted during the leftward head orientation condition than the baseline condition. With upward and downward directed head and gaze orientations, a similar effect was observed for neck and superior thoracic (i.e. C7T1-T4T5) flexion-extension. Interestingly, it was also demonstrated that changes in upward/downward head orientation can also change flexion-extension kinematics of the thoracolumbar region as well (i.e. T7T8-L1L2), suggesting that head postures requiring neck extension may also promote extension throughout these spine regions. These findings provide evidence for a functional link between changes in neck flexion-extension posture and flexion-extension movement of the thoracolumbar region of the spine.