Expression of neuropeptide Y and its receptors in the rat model of intervertebral disc degeneration induced by unbalanced dynamic and static forces and its correlation with pain threshold

Abstract:

Objective：To investigate the expression of neuropeptide Y（NPY），Y1 receptor（Y1R），and Y2 receptor（Y2R） in the inter－vertebral disc（IVD） and dorsal root ganglion（DRG） of rats with intervertebral disc degeneration（IDD） and sham-operated rats，and to investigate the correlation of NPY and its receptors with mechanical withdrawal threshold（MWT） and thermal withdrawal latency （TWL） in rats and the relationship of NPY and its receptors with discogenic low back pain. Methods：Twelve 6-month-old female specific pathogen-free Sprague-Dawley rats which were not pregnant were equally and randomly divided into two groups：IDD group and sham-operation group. An IDD model was induced by un－balanced dynamic and static forces in the IDD group，and sham operation was performed in the sham-operation group. At 12 weeks after the operation，whether the establishment of the IDD model was successful was evaluated by magnetic resonance imaging and X-ray，and MWT and TWL were measured. The expression of NPY and its receptors in the IVD and DRG was determined by immunohistochemistry to analyze the correlation of the mean optical density（MOD） of NPY and its receptors with pain behaviors（MWT and TWL）. Results：①Pain testing results showed that the IDD group had significantly lower MWT and TWL compared with the sham-operation group at 12 weeks after operation[（9.44±2.91） g vs. （17.99±4.40） g，P=0.002；（9.17±0.39） s vs. （13.53±1.69） s，P=0.002]. ②Immunohistochemical analysis showed that the IDD group had significantly higher expression of NPY in the IVD and DRG and significantly lower expression of Y1R in the IVD and DRG compared with the sham-operation group（IVD：0.15±0.03 vs. 0.11±0.02，P=0.021；DRG：0.23±0.04 vs. 0.17±0.04，P=0.018；IVD：0.10±0.02 vs. 0.13±0.01，P=0.009；DRG：0.05±0.01 vs. 0.08±0.01，P=0.000）. There was no signifi－cant difference in the expression of Y2R in the IVD and DRG between the two groups（P>0.05）. ③Pearson correlation analysis showed that the MOD values of NPY in the IVD and DRG were negatively correlated with MWT and TWL in the two groups（r=-0.605，P=0.037；r=-0.617，P=0.033；r=-0.603，P=0.038；r=-0.708，P=0.010）；the MOD values of Y1R in the IVD and DRG were positively correlated with MWT and TWL in the two groups（r=0.696，P=0.012；r=0.735，P=0.006；r=0.624，P=0.030；r=0.834，P=0.001）. Conclusion：In the rat model of unbalanced dynamic and static forces，NPY may be involved in the development and progression of discogenic low back pain through peripheral Y1R，but the specific mechanism needs further investigations.