Propofol ameliorates neuropathic pain and neuroinflammation through PPAR γ up-regulation to block Wnt/β-catenin pathway

OBJECTIVE: As an intravenous anesthetic, propofol has been exhibited to provide excellent clinical analgesia. Whether propofol has amelioration property for NP and neuroinflammation remains unexplored. The present study was arranged to probe the role of propofol in the mitigation of NP and neuroinflammation in rats and underlying mechanisms. METHODS: Rats were randomly classified into the following groups: Model, Sham, Control, Propofol, GW9662, and Saline groups. The radiant heat stimulation was used to measure paw withdrawal latency (PWL), and mechanical stimulation was employed to detect paw withdrawal threshold (PWT). Subsequently, the expression of GFAP was assessed by immunofluorescence to reflect the activation of astrocyte. qRT-PCR and Western blot were utilized for the performance of mRNA and protein expression levels of PPAR γ as well as inflammation factors (TNF-α, IL-1β, and IL-6). RESULTS: Pentobarbital sodium anesthesia significantly shortened the PWL and PWT, suppressed PPAR γ expression in rats in addition to elevating astrocyte activation and inflammation response. Propofol treatment attenuated the NP of rats as evidenced by restrained astrocyte activation level and inflammation factor levels. Rats treated with propofol had markedly heightened PPAR γ expression. PPAR γ exposure ameliorated NP and inflammation degree, which demonstrated by elevated astrocyte activation and inflammation levels as well as suppressed PWL and PWT in rats injected with PPAR γ inhibitor. Besides, PPAR γ decreased the expression level of β-catenin. CONCLUSION: Propofol ameliorates NP and neuroinflammation of rats by up-regulating PPAR γ expression to block the Wnt/β-catenin pathway.