title: Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain.
abstract: BACKGROUND
  Although electroacupuncture (EA) is effective in the relief of neuropathic pain, the underlying mechanisms remain unclear. Previous studies have reported immunomodulatory effects of EA in rats. Since excessive release of interferon-γ (IFN-γ) after nerve injury transforms quiescent spinal microglia into an activated state with more neuropathic pain, associated with purinergic receptor P2X4 expression, it is possible that EA may mediate its analgesic effect by attenuating IFN-γ release and subsequent generation of P2X4R(+) microglia.
  
  
  METHODS
  Male rats underwent chronic constriction injury (CCI) or IFN-γ intrathecal injection and von Frey tests were performed to evaluate the effect of EA on pain thresholds. Spinal IFN-γ and P2X4R expression levels were measured by immunohistochemistry, real-time PCR, enzyme immunoassay, and/or western blots. In vitro primary cultures of microglia were used to examine IFN-γ activation of P2X4R(+) cells.
  
  
  RESULTS
  In CCI rats, EA treatment significantly increased paw withdrawal threshold relative to control. IFN-γ facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA also down-regulated both P2X4R and IFN-γ expression in the spinal cord after CCI. However, EA did not exert the same analgesic effect after intrathecal IFN-γ injection.
  
  
  CONCLUSIONS
  EA ameliorated tactile allodynia after peripheral nerve injury by down-regulating excessive expression of IFN-γ in the spinal cord and subsequently reducing expression of P2X4R.
authors: Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: X-M
authors: XM
authors: Chen
authors: Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: J
authors: J
authors: Xu
authors: Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China songjg1993@126.com xiangruiwang2012@126.com.
authors: J-G
authors: JG
authors: Song
authors: Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: B-J
authors: BJ
authors: Zheng
authors: Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China songjg1993@126.com xiangruiwang2012@126.com.
authors: X-R
authors: XR
authors: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D006930:Hyperalgesia; D007124:Immunoenzyme Techniques / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D058848:Receptors, Purinergic P2X4; D007371:Interferon-gamma
keywords: P2X4 receptor; acupuncture; interferon-γ; neuropathic pain; spinal cord