Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons.
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.
Pertin
Marie
M
Anesthesiology Pain Research Group, Department of Anesthesiology, Lausanne University Hospital, CH-1011 Lausanne, Switzerland.
Ji
Ru-Rong
RR
Berta
Temugin
T
Powell
Andrew J
AJ
Karchewski
Laurie
L
Tate
Simon N
SN
Isom
Lori L
LL
Woolf
Clifford J
CJ
Gilliard
Nicolas
N
Spahn
Donat R
DR
Decosterd
Isabelle
I
D000818:Animals; D001522:Behavior, Animal; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism / Q000523:psychology; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D009443:Neuritis / Q000378:metabolism; D009463:Neuroma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D010543:Peroneal Nerve / Q000293:injuries; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000172:deficiency / Q000378:metabolism*; D013497:Sural Nerve / Q000378:metabolism; D013979:Tibial Nerve / Q000293:injuries; D015854:Up-Regulation; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; D014947:Wounds and Injuries / Q000150:complications / Q000378:metabolism
D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C117620:SCN2B protein, human; D015222:Sodium Channels; D062548:Voltage-Gated Sodium Channel beta-2 Subunit