Voltage-Gated Sodium Channel Expression in Mouse DRG after SNI Leads to Re-Evaluation of Projections of Injured Fibers

Autor: Isabelle Decosterd, Marie Pertin, Marc R Suter, Cédric J. Laedermann
Rok vydání: 2014
Předmět:
Nerve injury
SNi
Pathology
medicine.medical_specialty
Voltage-gated sodium channels (Navs)
Nerve fiber
Sural nerve
Voltage-Gated Sodium Channels
Activating transcription factor 3 (ATF3)
Sciatic nerve
Neuropathic pain
Mice
Spinal nerve ligation (SNL)
Cellular and Molecular Neuroscience
Ganglia
Spinal
medicine
Animals
Neurons
Afferent
Dorsal root ganglia (DRG)
Spared nerve injury (SNI)
Analysis of Variance
ATF3
Activating Transcription Factor 3
Lumbar Vertebrae
business.industry
Research
Sodium channel
Quantitative real time polymerase chain reaction (qRT-PCR)
Mice
Inbred C57BL
Activating Transcription Factor 3/metabolism
Disease Models
Animal
Ganglia
Spinal/metabolism
Ganglia
Spinal/pathology
Gene Expression Regulation/physiology
Hu Paraneoplastic Encephalomyelitis Antigens/metabolism
Neuralgia/metabolism
Neuralgia/pathology
Neurons
Afferent/metabolism
Neurons
Afferent/pathology
Sciatic Nerve/pathology
Spinal Nerves/injuries
Voltage-Gated Sodium Channels/genetics
Voltage-Gated Sodium Channels/metabolism
Spinal Nerves
Anesthesiology and Pain Medicine
medicine.anatomical_structure
ELAV Proteins
Gene Expression Regulation
nervous system
Neuralgia
Molecular Medicine
medicine.symptom
business
Neuroscience
Zdroj: Molecular Pain
Molecular Pain, vol. 10, pp. 19
ISSN: 1744-8069
DOI: 10.1186/1744-8069-10-19
Popis: BACKGROUND: Dysregulation of voltage-gated sodium channels (Na(v)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 Na(v)s under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Na(v)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 Na(v)s isoform expressed except for Na(v)1.2; even Na(v)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 Na(v)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 Na(v)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 Na(v)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.
Databáze: OpenAIRE
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