Comparison of vertebral and intervertebral disc lesions in aging humans and rhesus monkeys.

OBJECTIVE: To compare gross and histologic patterns of age-related degeneration within the intervertebral disc and adjacent vertebra between rhesus monkeys and humans. MATERIALS AND METHODS: We examined age-related patterns of disc degeneration from mid-sagittal sections of the intervertebral disc and adjacent vertebral bodies (VB) among six rhesus monkey thoracolumbar and seven human lumbar spines. Gross morphology and histopathology were assessed via the Thompson grading scheme and other degenerative features of the disc and adjacent bone. RESULTS: Thompson grades ranged from 3 through 5 for rhesus monkey discs (T9-L1) and 2 through 5 for the human discs (T12-S1). In both rhesus monkey and human discs, presence of distinct lesions was positively associated with Thompson grade of the overall segment. Degenerative patterns differed for radial tears, which were more prevalent with advanced disc degeneration in humans only. Additionally, compared to the more uniform anteroposterior disc degeneration patterns of humans, rhesus monkeys showed more severe osteophytosis and degeneration on the anterior border of the vertebral column. CONCLUSIONS: Rhesus monkey spines evaluated in the present study appear to develop age-related patterns of disc degeneration similar to humans. One exception is the absence of an association between radial tears and disc degeneration, which could reflect species-specific differences in posture and spinal curvature. Considering rhesus monkeys demonstrate similar patterns of disc degeneration, and age at a faster rate than humans, these findings suggest longitudinal studies of rhesus monkeys may be a valuable model for better understanding the progression of human age-related spinal osteoarthritis (OA) and disc degeneration.

The role of the vertebral end plate in low back pain.

End plates serve as the interface between rigid vertebral bodies and pliant intervertebral disks. Because the lumbar spine carries significant forces and disks don't have a dedicated blood supply, end plates must balance conflicting requirements of being strong to prevent vertebral fracture and porous to facilitate transport between disk cells and vertebral capillaries. Consequently, end plates are particularly susceptible to damage, which can increase communication between proinflammatory disk constituents and vascularized vertebral bone marrow. Damaged end plate regions can be sites of reactive bone marrow lesions that include proliferating nerves, which are susceptible to chemical sensitization and mechanical stimulation. Although several lines of evidence indicate that innervated end plate damage can be a source of chronic low back pain, its role in patients is likely underappreciated because innervated damage is poorly visualized with diagnostic imaging. This literature review summarizes end plate biophysical function and aspects of pathologic degeneration that can lead to vertebrogenic pain. Areas of future research are identified in the context of unmet clinical needs for patients with chronic low back pain.

Peripheral nerve lengthening by controlled isolated distraction: a new animal model.

We have developed a simple and effective animal model to study the distraction neurogenesis utilizing the sciatic nerve-lengthening technique in rats. The model allows macroscopic, physiological, and histological evaluation of the distraction site. Fourteen adult Harlan Sprague Dawley rats (300-350 g) were used in this study. A 10 mm segment of the right sciatic nerve of each animal in the nerve-lengthening group was resected. Gradual nerve lengthening was performed by advancing the proximal nerve stump at a rate of 1 mm/day. The proximal stump neuroma was then resected and a direct nerve anastomosis was performed. On the left side a standard autogenous nerve-grafting procedure was performed with a 10 mm segment of sciatic nerve used as an in situ nerve graft. Three months after the second surgery, the sciatic nerves were exposed and investigated by gross observation and EMG followed by histological processing and tissue analysis. Neomicrovascularization was observed surrounding the sciatic nerve anastomosis in all five specimens of the nerve-lengthening group as compared to the more white-colored scar tissue that was observed in the nerve-grafting group. The EMG results were similar for both groups. Histological studies of the lengthened nerves showed axon morphology equivalent to the grafted nerves. This study demonstrated a clear evidence of the successful nerve regeneration within a segmental nerve gap by nerve lengthening.

The effect of static in vivo bending on the murine intervertebral disc.

BACKGROUND CONTEXT: Intervertebral disc cell function in vitro has been linked to features of the local environment that can be related to deformation of the extracellular matrix. Epidemiologic data suggest that certain regimens of spinal loading accelerate disc degeneration in vivo. Yet, the direct association between disc cell function, spinal loading and ultimately tissue degeneration is poorly characterized. PURPOSE: To examine the relationships between tensile and compressive matrix strains, cell activity and annular degradation. STUDY DESIGN/SETTING: An in vivo study of the biologic, morphologic and biomechanical consequences of static bending applied to the murine intervertebral disc. SUBJECT SAMPLE: Twenty-five skeletally mature Swiss Webster mice (12-week-old males) were used in this study. OUTCOME MEASURES: Bending neutral zone, bending stiffness, yield point in bending, number of apoptotic cells, annular matrix organization, cell shape, aggrecan gene expression, and collagen II gene expression. METHODS: Mouse tail discs were loaded for 1 week in vivo with an external device that applied bending stresses. Mid-sagittal sections of the discs were analyzed for cell death, collagen II and aggrecan gene expression, and tissue organization. Biomechanical testing was also performed to measure the bending stiffness and strength. RESULTS: Forceful disc bending induced increased cell death, decreased aggrecan gene expression and decreased tissue organization preferentially on the concave side. By contrast, collagen II gene expression was symmetrically reduced. Asymmetric loading did not alter bending mechanical behavior of the discs. CONCLUSIONS: In this model, annular cell death was related to excessive matrix compression (as opposed to tension). Collagen II gene expression was most negatively influenced by the static nature of the loading (immobilization), rather than the specific state of stress (tension or compression).

Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study.

STUDY DESIGN: An in vivo study of the biologic and biomechanical consequences of static compressive loading on the mouse tail intervertebral disc. OBJECTIVES: To determine whether static compression in vivo alters the biologic activity of the disc and leads to diminished biomechanical performance. SUMMARY OF BACKGROUND DATA: Static compressive stress that exceeds the disc's swelling pressure is known to change hydration and the intradiscal stress distribution. Alterations in hydration and stress have been associated with changes in disc cell activity in vitro and in other collagenous tissues in vivo. METHODS: Mouse tail discs were loaded in vivo with an external compression device. After 1 week at one of three different stress levels, the discs were analyzed for their biomechanical performance, morphology, cell activity, and cell viability. A second group of mice were allowed to recuperate for 1 month after the 1-week loading protocol to assess the disc's ability to recover. As an aid to interpreting the histologic and biologic data, finite-element analysis was used to predict region-specific changes in tissue stress caused by the static loading regimen. RESULTS: With increasing compressive stress, the inner and middle anulus became progressively more disorganized, and the percentage of cells undergoing apoptosis increased. The expression of Type II collagen was suppressed at all levels of stress, whereas the expression of aggrecan decreased at the highest stress levels in apparent proportion to the decreased nuclear cellularity. Compression for 1 week did not affect the disc bending stiffness or strength but did increase the neutral zone by 33%. As suggested by the finite-element model, during sustained compression, tension is maintained in the outer anulus and lost in the inner and middle regions where the hydrostatic stress was predicted to increased nearly 10-fold. Discs loaded at the lowest stress recovered anular architecture but not cellularity after 1 month of recuperation. Discs loaded at the highest stress did not recover anular architecture, displaying islands of cartilage cells in the middle anulus at sites previously populated by fibroblasts. CONCLUSIONS: The results of the current project demonstrate that static compressive loading initiates a number of harmful responses in a dose-dependent way: disorganization of the anulus fibrosus; an increase in apoptosis and associated loss of cellularity; and down regulation of collagen II and aggrecan gene expression. The finite element model used in this study predicts loss of collagen fiber tension and increased matrix hydrostatic stress in those anular regions observed to undergo programmed cell death after 1 week of loading and ultimately become populated by chondrocytes after one month of recuperation. This correspondence conforms with the suggestions of others that the cellular phenotype in collagenous tissues is sensitive to the dominant type of tissue stress. Although the specific mechanisms by which alterations in tissue stress lead to apoptosis and variation in cell phenotype remain to be identified, our results suggest that maintenance of appropriate stress within the disc may be an important basis for strategies to mitigate disc degeneration and initiate disc repair.