title: Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain.
abstract: BACKGROUND
  Neuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG), spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain.
  
  
  RESULTS
  In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-kappaB p65 and production of proinflammatory cytokines (e.g., TNF-alpha and IL-1 beta).
  
  
  CONCLUSIONS
  These findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.
authors: Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China.
authors: Fei-xiang
authors: FX
authors: Wu
authors: Jin-jun
authors: JJ
authors: Bian
authors: Xue-rong
authors: XR
authors: Miao
authors: Sheng-dong
authors: SD
authors: Huang
authors: Xue-wu
authors: XW
authors: Xu
authors: De-jun
authors: DJ
authors: Gong
authors: Yu-ming
authors: YM
authors: Sun
authors: Zhi-jie
authors: ZJ
authors: Lu
authors: Wei-feng
authors: WF
authors: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000628:therapy*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha