Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain.
Changes in expression and function of voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons may play a major role in the genesis of peripheral hyperexcitability that occurs in neuropathic pain. We present here the first description of changes induced by spared nerve injury (SNI) to Na(v)1 mRNA levels and tetrodotoxin-sensitive and -resistant (TTX-S/TTX-R) Na(+) currents in injured and adjacent non-injured small DRG neurons. VGSC transcripts were down-regulated in injured neurons except for Na(v)1.3, which increased, while they were either unchanged or increased in non-injured neurons. TTX-R current densities were reduced in injured neurons and the voltage dependence of steady-state inactivation for TTX-R was positively shifted in injured and non-injured neurons. TTX-S current densities were not affected by SNI, while the rate of recovery from inactivation was accelerated in injured neurons. Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs.
Berta
Temugin
T
Department of Anesthesiology, University Hospital Center and University of Lausanne, CH-1011 Lausanne, Switzerland. temugin.berta@unil.ch
Poirot
Olivier
O
Pertin
Marie
M
Ji
Ru-Rong
RR
Kellenberger
Stephan
S
Decosterd
Isabelle
I
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005727:Ganglia, Spinal / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000235:genetics; D015640:Ion Channel Gating / Q000235:genetics*; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C568250:Scn1a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels