title: Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB.
abstract: BACKGROUND
  Treatment of neuropathic pain remains a challenge. The current study investigated the therapeutic effect of intrathecal administration of NF-kappaB antisense oligodeoxynucleotides (ODNs) on mechanical allodynia and thermal hyperalgesia in a chronic constriction injury (CCI) model of rats.
  
  
  METHODS
  Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats and a CCI model was established. Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency (PWL) to radiant heat and von Frey filaments. The phosphorothioate-modified antisense ODNs to p65 subunit of NF-kappaB were administered intrathecally on each of five consecutive days post-CCI. Nuclear NF-kappaB p65 expression was assessed by western blot.
  
  
  RESULTS
  CCI induced mechanical allodynia and thermal hyperalgesia and significantly increased NF-kappaB p65 protein expression. Intrathecal injection of antisense ODN markedly suppressed the expression of NF-kappaB p65 protein and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia.
  
  
  CONCLUSIONS
  The activation of NF-kappaB pathway may contribute to neuropathic pain in CCI rats. Suppression of NF-kappaB could be a potential new strategy for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: T
authors.initials: T
authors.lastname: Sun
authors.forename: W-G
authors.initials: WG
authors.lastname: Song
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Fu
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Liu
authors.forename: Y-M
authors.initials: YM
authors.lastname: Liu
authors.forename: S-L
authors.initials: SL
authors.lastname: Yao
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D015316:Genetic Therapy / Q000379:methods*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy; D007278:Injections, Spinal; D008297:Male; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D059408:Pain Management; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics* / Q000502:physiology
chemical_list: D016376:Oligonucleotides, Antisense; D051996:Transcription Factor RelA