Voltage-Gated Sodium Channel Expression in Mouse DRG after SNI Leads to Re-Evaluation of Projections of Injured Fibers. (11th March 2014)

• Record Type: Journal Article
• Authors: Laedermann, Cédric J; Pertin, Marie; Suter, Marc R; Decosterd, Isabelle
• Is Part Of: Molecular pain. Volume 10(2014)
• Publication Date: 2014-03-11
• Subjects: Activating transcription factor 3 (ATF3) -- Dorsal root ganglia (DRG) -- Nerve injury -- Neuropathic pain -- Quantitative real time polymerase chain reaction (qRT-PCR) -- Sciatic nerve -- Spared nerve injury (SNI) -- Spinal nerve ligation (SNL) -- Voltage-gated sodium channels (Navs); Pain -- Molecular aspects -- Periodicals; Pain -- Pathophysiology -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1186/1744-8069-10-19
• Languages: English
• ISSNs: 1744-8069

Abstract

Background: Dysregulation of voltage-gated sodium channels (Nav s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Nav s under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Nav s 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 Nav s isoform expressed except for Nav 1.2; even Nav 1.3, 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 Nav s 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 Nav s 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 Nav s, 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.