Continuous mechanical compression-induced intervertebral disc degeneration and pain in the caudal spine in rats

Abstract

Abstract Purpose Low back pain is a common disease with increasing incidence and disability rates that places an economic burden on families and society. Intervertebral disc degeneration (IVDD) is one of the main causes, but the mechanism of degeneration and pain has not been fully elucidated. Nonphysiological loading is one of the main causes of IVDD. This project aimed to establish a rat model of IVDD and low back pain and to preliminarily study the mechanism of P2Y2 receptor (P2Y2R)-mediated regulation of IVDD. Methods Fifty-six SPF male SD rats at 8 weeks of age were randomly divided into 4 groups: a 2-week control group, a 2-week experimental group, a 3-week control group, and a 3-week experimental group. The experimental groups were subjected to 8 N pressure for 2 and 3 weeks using the Ilizarov device, while the control groups were not subjected to pressure. MRI and HE and SO-FG staining were used to detect the degree of intervertebral disc degeneration in each group of rats after modeling. Von Frey filaments were used to detect the mechanical pain behavior of rats in each group before modeling (Pro) and on the 3rd, 6th, 9th, 12th, and 15th days after removal of the Ilizarov device. Immunofluorescence analysis and Western blotting were used to detect the expression levels of P2Y2R, YAP and TAZ in the nucleus pulposus tissue of humans or rats with different degrees of degeneration. Results Compared to the control group, the 2-week experimental group showed a significant increase in intervertebral disc degeneration, which was further exacerbated in the 3-week experimental group. The mechanical pain threshold of the control group was significantly reduced on D3 compared to that in the Pro group but recovered to normal on D9, 12, and 15. However, the postoperative pain threshold of the experimental group was significantly reduced and remained at a lower level for 2 weeks after surgery compared to that in the Pro group. P2Y2R fluorescence expression was significantly enhanced in the IVDD group compared to the control group, and P2Y2R, YAP, and TAZ were coexpressed in the nucleus pulposus of humans and rats. As the degree of intervertebral disc degeneration increased, the protein expression of P2Y2R significantly increased, while the protein expression of YAP first increased and then decreased. Additionally, the protein expression of TAZ increased with increasing degeneration within a certain range. Conclusions Prolonged mechanical compression of the caudal spine in rats leads to disc degeneration and associated pain. Initial findings suggested that P2Y2R and YAP/TAZ, which are downstream components of the Hippo signaling pathway, may play a role in the development of disc degeneration. These observations provide a foundation for future research in this area.