Flurbiprofen axetil alleviates the effect of formalin-induced inflammatory pain on the cognitive function of rats with mild cognitive impairment through the AMPKα/NF-κB signaling pathway.

Background: Mild cognitive impairment (MCI) as a prestage of dementia shares the most risk factors with dementia. In the present study, we explored the effect of flurbiprofen axetil on reducing the response of the central nervous system to inflammatory factors and anti-inhibiting apoptosis with the aim of developing a formalin-induced inflammatory pain model using MCI rats. Methods: Rats were subjected to sham operation (Sham group) or formalin-induced inflammatory pain, with or without flurbiprofen axetil (10 mg/kg). MCI rats were administered D-galactose (1,000 mg/kg) for 7 days subcutaneously. Thereafter, formalin was injected subcutaneously into the hind paws of rats, while sham group was injected with only normal saline. In the formalin/flurbiprofen group (F/F group), flurbiprofen axetil was injected into the tail vein 15 min before formalin was given, and the formalin/saline group (F/S group) used normal saline instead of the drug for injection. The pain score was recorded, and the time-score curve was drawn. The escape latency time and the number of times crossing the platform were recorded. The expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), AMP-activated protein kinase-α (AMPKα), and nuclear factor-κB p65 (NF-κB p65) in hippocampal tissue was determined. Varying degrees of pathological changes in the hippocampal CA1 region were observed. Results: The II phase pain score of rats in the F/F group was lower than that of the F/S group rats (P<0.05). The evasion incubation period and the number of platform crossings increased in both the F/F group and the F/S group (P<0.05), and were more significant in the F/S group. The relative content of AMPKα increased sequentially in the 3 groups, and the difference between the two comparisons of each group was statistically significant (P<0.05). The relative content of IL-6, TNF-α and NF-κB in the F/S group was greater than that of the F/F group, and the difference was statistically significant (P<0.001). Pathological morphological observations can be seen that the phenomena of nuclear consolidation, deep staining, and neuronal apoptosis occur, and the F/S group is more obvious. Conclusions: Flurbiprofen axetil can reduce the inflammatory response and cognitive function of an inflammatory pain model using MCI rats through the AMPKα/NF-κB signaling pathway.