title: Intrathecal injection of JWH015 attenuates remifentanil-induced postoperative hyperalgesia by inhibiting activation of spinal glia in a rat model.
abstract: BACKGROUND
  Hyperalgesia and neuroinflammation are associated with glia, which consists of macroglia and microglia. In this study, we used a selective cannabinoid receptor type 2 (CB2) agonist JWH015 to investigate remifentanil-induced postoperative hyperalgesia.
  
  
  METHODS
  Mechanical allodynia and thermal hyperalgesia after postoperative hyperalgesia and intrathecal injection of JWH015 were assessed by the paw withdrawal mechanical threshold and paw withdrawal thermal latency tests. We used immunohistochemistry and immunoblotting to investigate the effect of JWH015 on CB2 receptor, NR2B subunits, activated glial cells, and proinflammatory cytokine expression in rats after remifentanil-induced postoperative hyperalgesia.
  
  
  RESULTS
  Postoperative hyperalgesia was induced by intraoperative infusion of remifentanil. Glial cells were activated, and expression levels of several genes were significantly increased, including interleukin 6, tumor necrosis factor α, CB2, and the NR2B subunit phosphorylated at Tyr-1472 (p-NR2B). Intrathecal injection of JWH015 significantly inhibited glial cell activation, suppressed expression of interleukin 6, tumor necrosis factor α, and p-NR2B, and stimulated CB2 expression, thus attenuating postoperative hyperalgesia. However, these phenomena were abolished in the group that was preadministered with AM630.
  
  
  CONCLUSIONS
  The activation of glia, the production of proinflammatory cytokines, and the expression of CB2 and p-NR2B in the spinal dorsal horn increase significantly during the process of remifentanil-induced hyperalgesia. These changes can be regulated by pretreatment with JWH015, which may be the main mechanism underlying the antihyperalgesia effects of JWH015.
authors.affiliation: From the Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing, Jiangsu province, China.
authors.forename: Yu'e
authors.initials: Y
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Liu
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
mesh_terms: D000779:Anesthetics, Local / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007150:Immunohistochemistry; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010149:Postoperative Pain / Q000139:chemically induced / Q000188:drug therapy*; D010766:Phosphorylation; D010880:Piperidines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000378:metabolism; D000077208:Remifentanil; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D063386:Cannabinoid Receptor Agonists; D016207:Cytokines; D007211:Indoles; D010880:Piperidines; D043885:Receptor, Cannabinoid, CB2; D016194:Receptors, N-Methyl-D-Aspartate; D000077208:Remifentanil; C402944:JHW 015