title: Glycemia-dependent nuclear factor κB activation contributes to mechanical allodynia in rats with chronic postischemia pain.
abstract: BACKGROUND
  Ischemia-reperfusion injury causes chronic postischemia pain (CPIP), and rats with higher glycemia during ischemia-reperfusion injury exhibit increased allodynia. Glycemia-induced elevation of nuclear factor κB (NFκB) may contribute to increased allodynia.
  
  
  METHODS
  Glycemia during a 3-h ischemia-reperfusion injury was manipulated by: normal feeding; or normal feeding with administration of insulin; dextrose; or insulin/dextrose. In these groups, NFκB was measured in ipsilateral hind paw muscle and spinal dorsal horn by enzyme-linked immunosorbent assay (ELISA), and SN50, an NFκB inhibitor, was administered to determine its differential antiallodynic effects depending on glycemia.
  
  
  RESULTS
  CPIP fed/insulin rats (12.03 ± 4.9 g, N = 6) had less allodynia than fed, fed/insulin/dextrose, and fed/dextrose rats (6.29 ± 3.37 g, N = 7; 4.57 ± 3.03 g, N = 6; 2.95 ± 1.10 g, N = 9), respectively. Compared with fed rats (0.209 ± 0.022 AU, N = 7), NFκB in ipsilateral plantar muscles was significantly lower for fed/insulin rats, and significantly higher for fed/dextrose rats (0.152 ± 0.053 AU, N = 6; 0.240 ± 0.057 AU, N = 7, respectively). Furthermore, NFκB in the dorsal horn of fed, fed/insulin/dextrose, and fed/dextrose rats (0.293 ± 0.049 AU; 0.267 ± 0.037 AU; 0.315 ± 0.015 AU, respectively, N = 6 for each) was significantly higher than in fed/insulin animals (0.267 ± 0.037 AU, N = 6). The antiallodynic SN50 dose-response curves of CPIP rats in the fed/insulin/dextrose, fed/dextrose, and fed conditions exhibited a rightward shift compared with the fed/insulin group. The threshold SN50 dose of CPIP fed/dextrose, fed/insulin/dextrose, and fed rats (328.94 ± 92.4 ng, 77.80 ± 44.50 ng, and 24.89 ± 17.20 ng, respectively) was higher than that for fed/insulin rats (4.06 ± 7.04 ng).
  
  
  CONCLUSIONS
  NFκB was activated in a glycemia-dependent manner in CPIP rats. Hypoglycemic rats were more sensitive to SN50 than rats with higher glycemia. The finding that SN50 reduces mechanical allodynia suggests that NFκB inhibitors might be useful for treating postischemia pain.
authors.affiliation: Department of Anesthesia, McGill University, Montreal, Quebec, Canada.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Ross-Huot
authors.forename: André
authors.initials: A
authors.lastname: Laferrière
authors.forename: Mina
authors.initials: M
authors.lastname: Khorashadi
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Coderre
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D059350:Chronic Pain / Q000097:blood / Q000209:etiology*; D006930:Hyperalgesia / Q000209:etiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications*; D045442:Rotarod Performance Test
chemical_list: D001786:Blood Glucose; D016328:NF-kappa B