title: Expression of the sodium channel beta3 subunit in injured human sensory neurons.
abstract: Voltage-gated sodium channel alpha-subunits play a key role in pain pathophysiology, and are modulated by beta-subunits. We previously reported that beta1- and beta2-subunits were decreased in human sensory neurons after spinal root avulsion injury. We have now detected, by immunohistochemistry, beta3-subunits in 82% of small/medium and 67% of large diameter sensory neurons in intact human dorsal root ganglia: 54% of beta3 small/medium neurons were NGF receptor trkA negative. Unlike beta1- and beta2, beta3-immunoreactivity did not decrease after avulsion injury, and the beta3:neurofilament ratio was significantly increased in proximal injured human nerves. beta3-subunit expression may thus be regulated differently from beta1, beta2 and Nav1.8. Targeting beta3 interactions with key alpha-subunits, particularly Nav1.3 and Nav1.8, may provide novel selective analgesics.
authors.affiliation: Peripheral Neuropathy Unit, Imperial College London, Area A, Ground Floor, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Casula
authors.forename: Paul
authors.initials: P
authors.lastname: Facer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Powell
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Kinghorn
authors.forename: Christopher
authors.initials: C
authors.lastname: Plumpton
authors.forename: Simon N
authors.initials: SN
authors.lastname: Tate
authors.forename: Chas
authors.initials: C
authors.lastname: Bountra
authors.forename: Rolfe
authors.initials: R
authors.lastname: Birch
authors.forename: Praveen
authors.initials: P
authors.lastname: Anand
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology* / Q000293:injuries; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D016900:Neurofilament Proteins; D021122:Protein Subunits; D015222:Sodium Channels