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Background <p>Chronic low back pain imposes substantial social and economic burdens due to its rising prevalence and associated disability. Intervertebral disc degeneration is the primary driver of discogenic back pain, though the mechanistic links between degenerative changes and persistent pain remain incompletely defined. Aberrant mechanical loading is recognised as a key trigger of disc degeneration. This work built a caudal spine compression rat model to explore how the P2Y2 receptor mediates load-induced disc degeneration and associated pain.</p> Methods <p>Fifty-six eight-week-old male laboratory rats were randomised into four cohorts: 2-week sham surgery, 2-week axial compression, 3-week sham surgery, and 3-week axial compression. An external fixator delivered 8&#xa0;N continuous caudal spine compression to experimental animals, while sham rats received identical implantation without compressive force. Degenerative severity was evaluated via magnetic resonance imaging and two histological staining protocols. Von Frey filament testing measured mechanical pain sensitivity at baseline and multiple time points after device removal. Immunofluorescence and Western blotting detected target protein levels within degenerative disc tissue collected from both human surgical patients and experimental rats.</p> Results <p>Intervertebral disc degeneration was markedly aggravated after two weeks of compression and worsened further with three weeks of sustained loading. Sham-operated rats only had transient mechanical hypersensitivity at day 3 and fully recovered by days 9–15. By contrast, compressed rats maintained persistently lowered pain thresholds over the whole observation window. The P2Y2 receptor was elevated in degenerative disc tissue and co-localised with YAP and TAZ in human and rat disc core cells. In human samples, receptor levels rose alongside advancing degeneration; YAP and TAZ were elevated in moderately degenerated tissue and decreased in severely degenerated specimens.</p> Conclusions <p>Prolonged mechanical compression of the rat caudal spine produces disc degeneration and pain. The findings suggest that the P2Y2 receptor and downstream Hippo pathway mediators YAP and TAZ are involved in the degenerative process, offering a basis for future mechanistic studies.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月22日

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  • Fei Chen,
  • Na Li,
  • Junjie Pu,
  • Yiling Deng,
  • Junhui Qi,
  • Fanyi Kong,
  • Jiayu Chen

摘要

Background

Chronic low back pain imposes substantial social and economic burdens due to its rising prevalence and associated disability. Intervertebral disc degeneration is the primary driver of discogenic back pain, though the mechanistic links between degenerative changes and persistent pain remain incompletely defined. Aberrant mechanical loading is recognised as a key trigger of disc degeneration. This work built a caudal spine compression rat model to explore how the P2Y2 receptor mediates load-induced disc degeneration and associated pain.

Methods

Fifty-six eight-week-old male laboratory rats were randomised into four cohorts: 2-week sham surgery, 2-week axial compression, 3-week sham surgery, and 3-week axial compression. An external fixator delivered 8 N continuous caudal spine compression to experimental animals, while sham rats received identical implantation without compressive force. Degenerative severity was evaluated via magnetic resonance imaging and two histological staining protocols. Von Frey filament testing measured mechanical pain sensitivity at baseline and multiple time points after device removal. Immunofluorescence and Western blotting detected target protein levels within degenerative disc tissue collected from both human surgical patients and experimental rats.

Results

Intervertebral disc degeneration was markedly aggravated after two weeks of compression and worsened further with three weeks of sustained loading. Sham-operated rats only had transient mechanical hypersensitivity at day 3 and fully recovered by days 9–15. By contrast, compressed rats maintained persistently lowered pain thresholds over the whole observation window. The P2Y2 receptor was elevated in degenerative disc tissue and co-localised with YAP and TAZ in human and rat disc core cells. In human samples, receptor levels rose alongside advancing degeneration; YAP and TAZ were elevated in moderately degenerated tissue and decreased in severely degenerated specimens.

Conclusions

Prolonged mechanical compression of the rat caudal spine produces disc degeneration and pain. The findings suggest that the P2Y2 receptor and downstream Hippo pathway mediators YAP and TAZ are involved in the degenerative process, offering a basis for future mechanistic studies.