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.