title: Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy.
abstract: BACKGROUND
  Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms Na(V)1.7 and Na(V)1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in Na(V)1.7 protein levels in DRG in vivo. To further evaluate the role of Na(V)α subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against Na(V)α subunits.
  
  
  RESULTS
  Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in Na(V)α subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia.
  
  
  CONCLUSIONS
  These data support the role of increased Na(V)α protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.
authors.affiliation: Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
authors.forename: Munmun
authors.initials: M
authors.lastname: Chattopadhyay
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Hao
authors.forename: Marina
authors.initials: M
authors.lastname: Mata
authors.forename: David J
authors.initials: DJ
authors.lastname: Fink
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003929:Diabetic Neuropathies / Q000628:therapy*; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs