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

Med Sci Monit. 2019 Dec 31:25:10190-10197. doi: 10.12659/MSM.918420.

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)-alpha, interleukin (IL)-1ß, and IL-6. Western blot and the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect levels of p38MAPK and NF-kappaB 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-alpha, IL-1ß, 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-kappaB (NF-kappaB) pathway and the NLRP3 inflammasome.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Freund's Adjuvant / adverse effects*
  • Inflammasomes / metabolism
  • Inflammation / drug therapy*
  • Inflammation / genetics*
  • Inflammation Mediators / blood
  • Injections, Subcutaneous
  • Male
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pain / drug therapy*
  • Pain / genetics*
  • Propofol / administration & dosage
  • Propofol / pharmacology
  • Propofol / therapeutic use*
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Inflammasomes
  • Inflammation Mediators
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Freund's Adjuvant
  • p38 Mitogen-Activated Protein Kinases
  • Propofol