Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain.
Previous studies have shown that transection of the sciatic nerve induces dramatic changes in sodium currents of axotomized dorsal root ganglion (DRG) neurons, which are paralleled by significant changes in the levels of transcripts of several sodium channels expressed in these neurons. Sodium currents that are resistant to tetrodotoxin (TTX-R) and the transcripts of two TTX-R sodium channels are significantly attenuated, while a rapidly repriming tetrodotoxin-sensitive (TTX-S) current emerges and the transcripts of alpha-III sodium channel, which produce a TTX-S current when expressed in oocytes, are up-regulated. We report here on changes in sodium currents and sodium channel transcripts in DRG neurons in the chronic constriction injury (CCI) model of neuropathic pain. CCI-induced changes in DRG neurons, 14 days post-surgery, mirror those of axotomy. Transcripts of NaN and SNS, two sensory neuron-specific TTX-R sodium channels, are significantly down-regulated as is the TTX-R sodium current, while transcripts of the TTX-S alpha-III sodium channel and a rapidly repriming TTX-S Na current are up-regulated in small diameter DRG neurons. These changes may provide at least a partial basis for the hyperexcitablity of DRG neurons that contributes to hyperalgesia in this model.
Dib-Hajj
Sulayman D
SD
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA PVA/EPVA Neuroscience Research Center and Rehabilitation Research Center, Veterans Affairs Medical Center, West Haven, CT 06516, USA Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Fjell
Jenny
J
Cummins
Theodore R
TR
Zheng
Zheng
Z
Fried
Kaj
K
LaMotte
Robert
R
Black
Joel A
JA
Waxman
Stephen G
SG
D000818:Animals; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism*; D017403:In Situ Hybridization; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; C023790:tetrodotoxin-binding protein; D013779:Tetrodotoxin