Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers

Molecular Pain

Isabelle Decosterd¹  Marc R Suter²  Marie Pertin²  Cédric J Laedermann² 

[1] Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland;Pain Center, Department of Anesthesiology, University Hospital Center and University of Lausanne, Lausanne 1011, Switzerland

关键词: Voltage-gated sodium channels (Na_vs);    Spinal nerve ligation (SNL);    Spared nerve injury (SNI);    Sciatic nerve;    Quantitative real time polymerase chain reaction (qRT-PCR);    Neuropathic pain;    Nerve injury;    Dorsal root ganglia (DRG);    Activating transcription factor 3 (ATF3);   

Others  :  861744
DOI  :  10.1186/1744-8069-10-19

 received in 2013-10-07, accepted in 2014-02-28,  发布年份 2014

【 摘 要 】

Background

Dysregulation of voltage-gated sodium channels (Na_vs) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Na_vs under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Na_vs mRNA levels in mouse dorsal root ganglia (DRG) were studied in the spared nerve injury (SNI) and spinal nerve ligation (SNL) models of neuropathic pain. In the SNI model, injured and non-injured neurons were intermingled in lumbar DRG, which were pooled to increase the tissue available for experiments.

Results

A strong downregulation was observed for every Na_vs isoform expressed except for Na_v1.2; even Na_v1.3, known to be upregulated in rat neuropathic pain models, was lower in the SNI mouse model. This suggests differences between these two species. In the SNL model, where the cell bodies of injured and non-injured fibers are anatomically separated between different DRG, most Na_vs were observed to be downregulated in the L5 DRG receiving axotomized fibers. Transcription was then investigated independently in the L3, L4 and L5 DRG in the SNI model, and an important downregulation of many Na_vs isoforms was observed in the L3 DRG, suggesting the presence of numerous injured neurons there after SNI. Consequently, the proportion of axotomized neurons in the L3, L4 and L5 DRG after SNI was characterized by studying the expression of activating transcription factor 3 (ATF3). Using this marker of nerve injury confirmed that most injured fibers find their cell bodies in the L3 and L4 DRG after SNI in C57BL/6 J mice; this contrasts with their L4 and L5 DRG localization in rats. The spared sural nerve, through which pain hypersensitivity is measured in behavioral studies, mostly projects into the L4 and L5 DRG.

Conclusions

The complex regulation of Na_vs, together with the anatomical rostral shift of the DRG harboring injured fibers in C57BL/6 J mice, emphasize that caution is necessary and preliminary anatomical experiments should be carried out for gene and protein expression studies after SNI in mouse strains.

【 授权许可】

   
2014 Laedermann et al.; licensee BioMed Central Ltd.

【 图 表 】

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