Pain behavior and phenotype in a modified anterior lumbar disc puncture mouse model

BackgroundAn experimental study was performed to improve the anterior approach model of intervertebral disc degeneration (IVDD).ObjectiveThe aims of this study were to investigate the anterior approach model of IVDD for the cause of death, phenotypes, and underlying mechanisms of low back pain in mice.MethodIn this study, we conducted an anterior puncture procedure on a cohort of 300 C57BL/6J mice that were 8 weeks old. Our investigation focused on exploring the causes of death in the study population (n = 300) and assessing the time-course changes in various parameters, including radiographical, histological, immunofluorescence, and immunohistochemistry analyses (n = 10). Additionally, we conducted behavioral assessments on a subset of the animals (n = 30).ResultsTransverse vertebral artery rupture is a major factor in surgical death. Radiographical analyses showed that the hydration of the nucleus pulposus began to decrease at 2 weeks after puncture and obviously disappeared over 4 weeks. 3D-CT showed that disc height was significantly decreased at 4 weeks. Osteophyte at the anterior vertebral rims was observed at 2 weeks after the puncture. As the time course increased, histological analyses showed progressive disruption of the destruction of the extracellular matrix and increased secretion of inflammatory cytokines and apoptosis. Behavioral signs of low back pain were increased between the puncture and sham groups at 4 weeks.ConclusionThe improvement of anterior intervertebral disc approach model in mice will be useful to investigate underlying mechanisms and potential therapeutic strategies for behavior and phenotypes. Furthermore, the application of vibrational pre-treatment can be used to increase the sensitivity of axial back pain in the model, thereby providing researchers with a reliable method for measuring this critical phenotype. Improvements to the anterior intervertebral disc approach model in mice have the potential to advance the investigation of underlying mechanisms and potential therapeutic strategies for a range of phenotypes and behavioral manifestations of IVDD. Furthermore, the application of vibrational pre-treatment can be used to increase the sensitivity of axial back pain in the model, thereby providing researchers with a reliable method for measuring this critical phenotype. The identification of such techniques may have significant implications for the development of new therapeutic interventions to manage IVDD and associated LBP.image