Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons

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Version: Final published version
Serval ID
serval:BIB_0E574A1B52D3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons
Journal
Journal of Neuroscience
Author(s)
Pertin  M., Ji  R. R., Berta  T., Powell  A. J., Karchewski  L., Tate  S. N., Isom  L. L., Woolf  C. J., Gilliard  N., Spahn  D. R., Decosterd  I.
ISSN
1529-2401 (Electronic)
Publication state
Published
Issued date
11/2005
Volume
25
Number
47
Pages
10970-80
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Nov 23
Abstract
The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression of voltage-gated sodium channels (VGSCs) and a modification of sodium currents. To investigate whether the beta2 subunit of VGSCs participates in the generation of neuropathic pain, we used the spared nerve injury (SNI) model in rats to examine beta2 subunit expression in selectively injured (tibial and common peroneal nerves) and uninjured (sural nerve) afferents. Three days after SNI, immunohistochemistry and Western blot analysis reveal an increase in the beta2 subunit in both the cell body and peripheral axons of injured neurons. The increase persists for >4 weeks, although beta2 subunit mRNA measured by real-time reverse transcription-PCR and in situ hybridization remains unchanged. Although injured neurons show the most marked upregulation,beta2 subunit expression is also increased in neighboring non-injured neurons and a similar pattern of changes appears in the spinal nerve ligation model of neuropathic pain. That increased beta2 subunit expression in sensory neurons after nerve injury is functionally significant, as demonstrated by our finding that the development of mechanical allodynia-like behavior in the SNI model is attenuated in beta2 subunit null mutant mice. Through its role in regulating the density of mature VGSC complexes in the plasma membrane and modulating channel gating, the beta2 subunit may play a key role in the development of ectopic activity in injured and non-injured sensory afferents and, thereby, neuropathic pain.
Keywords
Animals Behavior, Animal Electrophysiology Ganglia, Spinal/metabolism Hyperalgesia/metabolism/psychology Ion Channel Gating/*physiology Male Mice Mice, Knockout Nerve Tissue Proteins/deficiency/*metabolism Neuralgia/etiology/*metabolism Neuritis/metabolism Neuroma/metabolism Neurons/metabolism Neurons, Afferent/*metabolism Peroneal Nerve/injuries Protein Isoforms/metabolism Rats Rats, Sprague-Dawley Sodium Channels/deficiency/*metabolism Sural Nerve/metabolism Tibial Nerve/injuries Up-Regulation Wounds and Injuries/complications/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 10:45
Last modification date
20/08/2019 12:35
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