title: Involvement of EphB1 receptor/EphrinB2 ligand in neuropathic pain.
abstract: METHODS
  We investigated involvement of EphB/ephrinB system in neuropathic pain.
  
  
  OBJECTIVE
  Using immunoblotting, immunohistochemistry, and RNA interference techniques, we examined the expression levels of EphB receptors and ephrinB ligands in neuropathic pain. We also explored the effect of ephrinB siRNA for neuropathic pain.
  
  
  BACKGROUND
  It has been reported that EphB2 regulates the development of synaptic plasticity in the hippocampus by interacting with N-methyl-D-aspartate (NMDA) receptors. In acute pain models, it has been clear that EphB1/ephrinB2 interactions via the NMDA receptor modulates synaptic efficacy in spinal cord.
  
  
  METHODS
  Adult female Sprague-Dawley rats were used in this study. A crush injury model was prepared by crushing the left L5 spinal nerve distal to dorsal root ganglions (DRG) under deep anesthesia. The sham operation was subjected as control. Expression of ephrinB2 and EphB1 were examined by immunoblotting and immunohistochemical analyses with anti-EphB and anti-ephrinB antibodies. To assess involvement of ephrinB in neuropathic pain, we examined the effect of small interference RNA (siRNA) on mechanical allodynia.
  
  
  RESULTS
  Among EphB and ephrinB isoforms tested, ephrinB2 and EphB1 were predominant in DRG and spinal cord. Results showed that the expression of ephrinB2 was enhanced in neurons in DRG and spinal cord by the injury in a time-dependent manner. EphB1 was expressed in neurons of spinal cord. Administration of ephrinB2 siRNA reduced the expression of ephrinB2 and mechanical allodynia.
  
  
  CONCLUSIONS
  Expression of ephrinB2 is enhanced by nerve injury in neurons in DRG and spinal cord, while its receptor EphB1 is expressed in spinal cord. These results suggest that induction of ephrinB2 might activate EphB1/ephrinB2 signaling pathway to regulate synaptic plasticity and reorganization, and that ephrinB2 siRNA could be a potential therapeutic agent for neuropathic pain.
authors.affiliation: Department of Orthopaedic Surgery and Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitamura
authors.forename: Miho
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Miwako K
authors.initials: MK
authors.lastname: Homma
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Kabuyama
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Konno
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D036388:Ephrin-B2 / Q000378:metabolism*; D005260:Female; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D036225:Receptor, EphB1 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
chemical_list: D036388:Ephrin-B2; D034741:RNA, Small Interfering; D036225:Receptor, EphB1