title: Effect of adenosine triphosphate-sensitive potassium activation on peripheral and central pain sensitization.
abstract: BACKGROUND
  Alterations in adenosine triphosphate-sensitive potassium (KATP) activity and expression under changing physiological conditions are important adaptive and protective mechanisms. KATP subunit expression is also altered in neuropathic pain; whether these changes are adaptive or deleterious is unclear. We therefore established a skin/muscle incision and retraction (SMIR) rat model of postoperative pain and examined the relationship between pain sensitization and changes in KATP subunit expression.
  
  
  METHODS
  Rats were randomly divided into untreated, sham-operation, SMIR, and SMIR + Pinacidil (sulfonylurea receptor [SUR]2-activator) groups. In the SMIR group, skin and muscle were retracted for 1 h after incision. In the SMIR + Pinacidil group, Pinacidil was injected intraperitoneally 0.5 h before SMIR or into the spinal myelin sheath 7 d after SMIR. Mechanical withdrawal threshold was used as an index of pain sensitivity. Expression levels and localization of the KATP subunits Kir6.2, Kir6.1, SUR1, and SUR2 were measured by Western blotting and immunofluorescence.
  
  
  RESULTS
  A rat postoperative pain model was successfully established, in which SMIR induced mechanical hypersensitivity (allodynia). Notably, significantly increased Kir6.1, Kir6.2, SUR1, and SUR2 protein expression levels were observed in tissues around the incision (P < 0.05). In addition, significantly decreased Kir6.1, SUR2, and SUR1 protein levels were obtained in spinal cord L3-L5. SMIR also starkly increased nerve growth factor expression in the muscle around the incision. Importantly, intrathecal Pinacidil injection inhibited the overexpression of allodynia markers and nerve growth factor.
  
  
  CONCLUSIONS
  Hyperexcitability due to spinal Kir6.1 and SUR2 downregulation may be responsible for postoperative pain. SUR2 activation is a potential strategy to inhibit postoperative allodynia.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Shiren
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China. Electronic address: cao112138353@163.com.
authors.forename: Su
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Saisai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Nantong University, Nantong, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000503:physiopathology; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D010149:Postoperative Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064233:Sulfonylurea Receptors / Q000502:physiology
chemical_list: C577509:Abcc8 protein, rat; C577512:Abcc9 protein, rat; D054086:KATP Channels; D064233:Sulfonylurea Receptors
keywords: K(ATP) subunit; Pain sensitization; SMIR