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31 December 2019 : Animal Research  

The Molecular Mechanisms Associated with the Effects of Propofol in a Rat Model of Pain Due to Inflammation Following Injection with Complete Freund’s Adjuvant

Shanshan Tan1ABCDEFG, He Liu2BCD, Yuanzheng Wang3BD, Shanshan Zhu3ACEG*

DOI: 10.12659/MSM.918420

Med Sci Monit 2019; 25:10190-10197

Abstract

BACKGROUND: This study aimed to investigate the molecular mechanisms associated with the effects of propofol in a rat model of pain due to inflammation following subcutaneous injection with complete Freund’s adjuvant (CFA).

MATERIAL AND METHODS: Sprague-Dawley rats were injected subcutaneously in the paw with CFA. Propofol or saline was administered by tail vein injection. After CFA treatment for 0 hours, 4 hours, 1 day, 4 days, 7 days, and 14 days, the behavior of the rats was assessed. An enzyme-linked immunosorbent assay (ELISA) measured serum levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Western blot and the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect levels of p38MAPK and NF-κB related mRNA and proteins, including p-p38, p38, p65, p-p65, NOD-like receptor family protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and caspase-1 in rat spinal cord tissues.

RESULTS: Injection of CFA significantly reduced the mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and frequency responses to cold stimulation. Propofol treatment significantly reduced serum levels of TNF-α, IL-1β, and IL-6. Protein expression levels of p-p38 and p-p65 were upregulated in the rat model, which were inhibited by propofol treatment. CFA injection increased the expression levels of NLRP3, ASC, and caspase-1 in the spinal cord tissues of rats, which were reduced by propofol treatment.

CONCLUSIONS: In a rat model of pain following subcutanous injection with CFA, propofol reduced CFA-induced pain and inhibited the inflammatory response through the p38MAPK-nuclear factor-κB (NF-κB) pathway and the NLRP3 inflammasome.

Keywords: MAP Kinase Kinase Kinases, NF-kappa B, Pain, Propofol, Behavior, Animal, Freund's Adjuvant, Inflammasomes, Inflammation Mediators, Injections, Subcutaneous, NLR Family, Pyrin Domain-Containing 3 Protein, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750