Upregulation of the Voltage-Gated Sodium Channel β2 Subunit in Neuropathic Pain Models: Characterization of Expression in Injured and Non-Injured Primary Sensory Neurons

Autor: Isabelle Decosterd, Ru-Rong Ji, Clifford J. Woolf, Marie Pertin, Temugin Berta, Nicolas Gilliard, Laurie A. Karchewski, Donat R. Spahn, Simon Tate, Lori L. Isom, Andrew J. Powell
Rok vydání: 2005
Předmět:
Male
SNi
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
Protein subunit
Development/Plasticity/Repair
Nerve Tissue Proteins
Sural nerve
In situ hybridization
Sodium Channels
Rats
Sprague-Dawley
Mice
Neuroma
Neuritis
Sural Nerve
Ganglia
Spinal
Animals
Protein Isoforms
Medicine
Neurons
Afferent
Mice
Knockout
Neurons
Behavior
Animal
Voltage-Gated Sodium Channel beta-2 Subunit
business.industry
General Neuroscience
Sodium channel
Peroneal Nerve
Nerve injury
Rats
Up-Regulation
Electrophysiology
Hyperalgesia
Neuropathic pain
Peripheral nerve injury
Neuralgia
Wounds and Injuries
Tibial Nerve
medicine.symptom
business
Ion Channel Gating
Neuroscience
Zdroj: Journal of Neuroscience, vol. 25, no. 47, pp. 10970-80
ISSN: 1529-2401
0270-6474
Popis: 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 β2 subunit of VGSCs participates in the generation of neuropathic pain, we used the spared nerve injury (SNI) model in rats to examine β2 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 β2 subunit in both the cell body and peripheral axons of injured neurons. The increase persists for >4 weeks, although β2 subunit mRNA measured by real-time reverse transcription-PCR andin situhybridization remains unchanged. Although injured neurons show the most marked upregulation,β2 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 β2 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 β2 subunit null mutant mice. Through its role in regulating the density of mature VGSC complexes in the plasma membrane and modulating channel gating, the β2 subunit may play a key role in the development of ectopic activity in injured and non-injured sensory afferents and, thereby, neuropathic pain.
Databáze: OpenAIRE
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