Propofol partially attenuates complete freund's adjuvant-induced neuroinflammation through inhibition of the ERK1/2/NF-κB pathway

Abstract

Peripheral inflammation in male C57BL/6 mice was induced by intraplantar injection of 20 μL complete freund's adjuvant (CFA) in the left hind paw. Mice were randomly divided into three groups: Sham, CFA, and propofol+CFA. Mechanical allodynia was assessed by von Frey analysis, and heat hyperalgesia was detected by exposure of the plantar surface to a beam of radiant heat. Propofol significantly attenuated the severity and duration of CFA-induced pain hypersensitivity, heat hyperalgesia, and paw edema. Propofol inhibited CFA-induced microglia activation, and markedly decreased CFA-induced ionized calcium binding adapter molecule 1 (IBA-1) expression. Propofol inhibited CFA-induced expression of p-extracellular signal-regulated kinase1/2 (p-ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, as demonstrated by Western blot analysis. In addition, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays indicated that propofol had no cytotoxic effect on BV2 microglia cells. Reverse transcription-quantitative-polymerase chain reaction and enzyme-linked immunosorbent assay results demonstrated that propofol attenuates CFA-induced tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β production in the spinal cord as well as in BV2 cells. Taken together, these results demonstrate that propofol attenuates CFA-induced neuroinflammation (TNF-α, IL-6, and IL-1β expression) through a mechanism that involves activation of ERK1/2/NF-κB signaling pathway.

Keywords: extracellular signal-regulated kinase1/2/nuclear factor kappa-light-chain-enhancer of activated B cells (ERK1/2/NF-κB) pathway; neuroinflammation; propofol.