title: Expression changes of microRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are involved in the neuroplastic changes which induce and maintain neuropathic pain. However, it is unknown whether nerve injury leads to altered miRNA expression and modulation of pain relevant target gene expression within peripheral nerves. In the present study, expression profiles of miR-1 and the pain-relevant targets, brain derived neurotrophic factor (BDNF) and Connexin 43 (Cx43), were studied in peripheral neuropathic pain, which was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. The expression of miR-1 was investigated in the sciatic nerve, dorsal root ganglion (DRG) and the ipsilateral spinal cord by qPCR. Changes of BDNF and Cx43 expression patterns were studied using qPCR, Western blot analysis, ELISA and immunohistochemistry.
  
  
  RESULTS
  In sciatic nerves of naïve rats, expression levels of miR-1 were more than twice as high as in DRG and spinal cord. In neuropathic rats, CCI lead to a time-dependent downregulation of miR-1 in the sciatic nerve but not in DRG and spinal cord. Likewise, protein expression of the miR-1 targets BDNF and Cx43 was upregulated in the sciatic nerve and DRG after CCI. Immunohistochemical staining revealed an endoneural abundancy of Cx43 in injured sciatic nerves which was absent after Sham operation.
  
  
  CONCLUSIONS
  This study demonstrates that CCI leads to a regulation of miRNAs (miR-1) in the peripheral nervous system. This regulation is associated with alterations in the expression and localization of the miR-1 dependent pain-relevant proteins BDNF and Cx43. Further studies will have to explore the function of miRNAs in the context of neuropathic pain in the peripheral nervous system.
authors.affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. Elena.neumann@med.uni-duesseldorf.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
authors.affiliation: Department of Anesthesiology, Academic Medical Center, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands. h.hermanns@amc.uva.nl.
authors.forename: Henning
authors.initials: H
authors.lastname: Hermanns
authors.affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. franziska_barthel@hotmail.com.
authors.forename: Franziska
authors.initials: F
authors.lastname: Barthel
authors.affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. robert.werdehausen@med.uni-duesseldorf.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Werdehausen
authors.affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. timo.brandenburger@med.uni-duesseldorf.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Brandenburger
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D003250:Constriction; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009437:Neuralgia / Q000150:complications / Q000235:genetics*; D017933:Peripheral Nervous System / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018031:Connexin 43; C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger