title: Voltage-gated sodium channel function and expression in injured and uninjured rat dorsal root ganglia neurons.
abstract: The nine members of the voltage-gated sodium channel (Nav) family mediate inward sodium currents that depolarize neurons and lead to action potential firing. Increased Nav expression and function in sensory ganglia may drive ectopic action potentials and result in neuropathic pain. Using patch-clamp electrophysiology and molecular biology techniques, experiments were performed to elucidate the contribution of Nav channels to sodium currents in rat dorsal root ganglion (DRG) neurons following the L5/L6 spinal nerve ligation (SNL) model of neuropathic pain. The abundance of DRG neurons with fast, tetrodotoxin sensitive (TTX-S) currents was seven-fold higher whereas the abundance of DRG neurons with slow, tetrodotoxin resistant (TTX-R) currents was nearly thirty-fold lower when comparing ipsilateral (injured) to contralateral (uninjured) neurons. TTX-S currents were elevated in larger neurons while TTX-R currents were reduced in both small and large neurons. Among Nav transcripts encoding TTX-R channels, Scn10a (Nav1.8) and Scn11a (Nav1.9) expression was twenty- to thirty-fold lower, while among Nav transcripts encoding TTX-S channels, Scn3a (Nav1.3) expression was four-fold higher in injured compared to uninjured DRG by qRT-PCR analysis. In summary, the SNL model of neuropathic pain induced a phenotypic switch in Nav expression from TTX-R to TTX-S channels in injured DRG neurons. Transcriptional reprogramming of Nav genes may drive ectopic action potential firing and contribute to neuropathic pain.
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.|b Department of Neuroscience, Amgen Inc. , South San Francisco, CA, USA.
authors.forename: Ruoyuan
authors.initials: R
authors.lastname: Yin
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: c Department of Protein Technologies, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Chhoa
authors.affiliation: c Department of Protein Technologies, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Li
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Sonya G
authors.initials: SG
authors.lastname: Lehto
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Immke
authors.affiliation: a Department of Neuroscience, Amgen Inc. , Thousand Oaks, CA, USA.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Moyer
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects; D004558:Electric Stimulation; D007839:Functional Laterality / Q000502:physiology*; D005727:Ganglia, Spinal / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D059348:Peripheral Nerve Injuries / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D013779:Tetrodotoxin
keywords: Nav; electrophysiology; neuropathic pain; tetrodotoxin; transcription