title: Electroacupuncture Relieves Nerve Injury-Induced Pain Hypersensitivity via the Inhibition of Spinal P2X7 Receptor-Positive Microglia.
abstract: BACKGROUND
  Electroacupuncture (EA) has therapeutic effects on neuropathic pain induced by nerve injury; however, the underlying mechanisms remain unclear. In this study, we examined whether EA treatment relieves pain hypersensitivity via the down-regulation of spinal P2X7 receptor-positive (P2X7R⁺) microglia-mediated overexpression of interleukin (IL)-1β and/or IL-18.
  
  
  METHODS
  Male Sprague-Dawley rats underwent chronic constriction injury (CCI) or 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) intrathecal injection. Von Frey and Hargreaves tests were performed to evaluate the effect of EA on pain hypersensitivity. The spinal P2X7R, IL-1β, and IL-18 expression levels were determined by real-time polymerase chain reaction, Western blot analysis, immunofluorescence staining, and enzyme-linked immunosorbent assay. The selective P2X7R antagonist A-438079 was used to examine the P2X7R⁺ microglia-dependent release of IL-1β and IL-18. Primary cultures were subsequently used to assess the P2X7R⁺ microglia-induced IL-1β and IL-18 release.
  
  
  RESULTS
  EA treatment significantly improved the pain thresholds and inhibited spinal P2X7R⁺ microglia activation induced by CCI or BzATP administration, which was accompanied by the suppression of spinal IL-1β and IL-18 overexpression. Moreover, A-438079 also improved pain thresholds and suppressed overexpression of IL-1β in the CCI- and BzATP-injected rats. The analysis of cultured microglia further demonstrated that A-438079 markedly decreased BzATP-induced IL-1β release.
  
  
  CONCLUSIONS
  EA treatment relieves nerve injury-induced tactile allodynia and thermal hyperalgesia via the inhibition of P2X7R⁺ microglia-mediated IL-1β overexpression.
authors.affiliation: From the Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Chen
authors.forename: Bei-Jie
authors.initials: BJ
authors.lastname: Zheng
authors.forename: Xiang-Rui
authors.initials: XR
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D015671:Electroacupuncture; D006930:Hyperalgesia / Q000628:therapy*; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D017628:Microglia; D009437:Neuralgia / Q000628:therapy*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects; D013116:Spinal Cord; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; C000594089:IL1B protein, rat; D020382:Interleukin-18; D053583:Interleukin-1beta; D058920:Purinergic P2X Receptor Antagonists; D011725:Pyridines; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate