RT Journal Article
SR Electronic
T1 Upregulation of the Voltage-Gated Sodium Channel β2 Subunit in Neuropathic Pain Models: Characterization of Expression in Injured and Non-Injured Primary Sensory Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10970
OP 10980
DO 10.1523/JNEUROSCI.3066-05.2005
VO 25
IS 47
A1 Marie Pertin
A1 Ru-Rong Ji
A1 Temugin Berta
A1 Andrew J. Powell
A1 Laurie Karchewski
A1 Simon N. Tate
A1 Lori L. Isom
A1 Clifford J. Woolf
A1 Nicolas Gilliard
A1 Donat R. Spahn
A1 Isabelle Decosterd
YR 2005
UL http://www.jneurosci.org/content/25/47/10970.abstract
AB 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 and in situ hybridization 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.