Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner

Abstract

Background During recent decades, the knowledge of the pathophysiology of disc herniation and sciatica has drastically improved. What previously was considered a strict biomechanical process is now considered a more complex interaction between leaked nucleus pulposus and the tissue in the spinal canal. An inflammatory reaction, with tumor necrosis factor (TNF) playing an essential role, has been demonstrated. However, the exact mechanisms of the pathophysiology of disc herniation remain unknown. Questions/purposes In this study we use an animal model to investigate (1) if and/or how experimental disc herniation affects gene expression in the early phase (24 hours postsurgery) in the dorsal root ganglion; and (2) if TNF inhibition can reduce any observed changes. Methods A rat model of disc herniation was used. Twenty rats were evenly divided into four groups: naïve, sham, disc herniation, and disc herniation with TNF inhibition. The dorsal root ganglion of the affected nerve root was harvested 24 hours after surgery and analyzed with a TaqMan Low Density Array 1 quantitative polymerase chain reaction assay. Gene expression levels in sham were compared with disc herniation to assess question 1 and disc herniation to disc herniation with TNF inhibition to assess question 2. Results Experimental disc herniation caused a decrease in the expression of the serotonin receptor 2c gene (p = 0.022). TNF inhibition was found to reduce the observed decrease in expression of serotonin receptor 2c (p = 0.037). Conclusions Our results suggest that a decrease in the expression of the serotonin receptor 2c gene may contribute to the pathophysiology of disc herniation. Further research on its involvement is warranted. Clinical Relevance This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may

Characterization of pain-related behaviors in a rat model of acute-to-chronic low back pain: single vs. multi-level disc injury

“…Histologically, the punctured IVDs from both DP groups showed radiological and histological signs of degeneration at 18 weeks post-injury. Similar histopathology was observed in the punctured IVDs for both DP groups, including: fibrosis of the nucleus pulposus [also termed granulation ( 19 )], annulus fibrosis layer disruption and moderate bulging (avoiding complete disc herniation), and merging of the normally separate interface between the nucleus pulposus and annulus fibrosis, each a sign of disc degeneration in rodents ( 13 , 89 ). It was our intent to perform a moderate IVD injury with a slower progressive degeneration than observed in models using larger needles, deeper insertion of needles, and/or approaches that displace adjacent nerve roots, as these methods can result in complete disc rupture as early as 24 h after surgery ( 19 , 27 , 90 ), which is a far less common clinical scenario.…”