Intervertebral disc degeneration induced by long-segment in-situ immobilization: A macro, micro, and nanoscale analysis

Abstract

Background: Cervical spine fixation or immobilization has become a routine treatment for spinal fracture, dislocation, subluxation injuries, or spondylosis. The effects of immobilization of intervertebral discs of the cervical spine is unclear. The goal of this study was to evaluate the effects of long-segment in-situ immobilization of intervertebral discs of the caudal vertebra, thereby simulating human cervical spine immobilization. Methods: Thirty-five fully grown, male Sprague-Dawley rats were used. Rats were randomly assigned to one of five groups: Group A, which served as controls, and Groups B, C, D, and E, in which the caudal vertebrae were in-situ immobilized using a custom-made external device that fixed four caudal vertebrae (Co7-Co10). After 2 weeks, 4 weeks, 6 weeks, and 8 weeks of in-situ immobilization, the caudal vertebrae were harvested, and the disc height, the T2 signal intensity of the discs, disc morphology, the gene expression of discs, and the structure and the elastic modulus of discs was measured. Results: The intervertebral disc height progressively decreased, starting at the 6th week. At week 6 and week 8, disc degeneration was classified as grade III, according to the modified Pfirrmann grading system criteria. Long-segment immobilization altered the gene expression of discs. The nucleus pulposus showed a typical cell cluster phenomenon over time. The annulus fibrosus inner layer began to appear disordered with fissure formation. The elastic modulus of collagen fibrils within the nucleus pulposus was significantly decreased in rats in group E compared to rats in group A (p < 0.05). On the contrary, the elastic modulus within the annulus was significantly increased in rats in group E compared to rats in group A (p < 0.05). Conclusion: Long-segment in-situ immobilization caused target disc degeneration, and positively correlated with fixation time. The degeneration was not only associated with changes at the macroscale and microscale, but also indicated changes in collagen fibrils at the nanoscale. Long-segment immobilization of the spine (cervical spine) does not seem to be an innocuous strategy for the treatment of spine-related diseases and may be a predisposing factor in the development of the symptomatic spine.