Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner
- 279 Downloads
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.
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.
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® 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.
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).
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.
This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may contribute to the development of more and better treatment options for patients with disc herniation and sciatica.
KeywordsDorsal Root Ganglion Nucleus Pulposus Disc Herniation Tumor Necrosis Factor Inhibition Disc Puncture
- 1.Andersen CL, Jensen JL, Orntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 2004;64:5245–5250.CrossRefPubMedGoogle Scholar
- 9.Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, Bowman C, Hammond A, Kirkham B, Jarvinen S, Niinimaki J, Veeger N, Haapea M, Torkki M, Tervonen O, Seitsalo S, Hurri H. The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial. Spine. 2006;31:2759–2766.CrossRefPubMedGoogle Scholar
- 13.Nachemson A, Jonsson E. [Backache and Neck Pain—An Evidence-based Review of Causes, Diagnostics and Treatments] [in Swedish]. Stockholm, Sweden: SBU, Swedish Council on Health Technology Assessment; 2000.Google Scholar
- 16.Olmarker K, Rydevik B. Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity: possible implications for future pharmacologic treatment strategies of sciatica. Spine. 2001;26:863–869.CrossRefPubMedGoogle Scholar
- 18.Saito H, Wakai J, Sekiguchi M, Kikuchi S, Konno S. The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain. Eur Spine J. 2014 Jun 5 [Epub ahead of print].Google Scholar