Background and aims: Bacterial LPS causes inflammation leading to decreased pain threshold or increased pain sensitivity termed as hyperalgesia. The aim of this study was to determine effect of a selective RXRα agonist, bexarotene, on TLR4/MyD88/TAK1/NF-κB/COX-2 signaling pathway in relation to proinflammatory cytokine expression in the central nervous system in LPS-induced hyperalgesia in mice. 
Methods: Male Balb/c mice were divided into 5 groups: (1) Saline, (2) LPS, (3) DMSO, (4) bexarotene, and (5) LPS+bexarotene. DMSO (1%; 4 ml/kg) or bexarotene (10 mg/kg) were injected simultaneously with saline (10 ml/kg) or LPS (10 mg/kg). Following determination of reaction time to thermal stimuli within 30 s 6 h after injection, the mice were euthanized. Brains and spinal cords were collected from the animals for measurement of TLR4, MyD88, TAK1, phosphorylated TAK1, NF-κB, phosphorylated NF-κB, COX-2, IL-1β, RXRα, and β-tubulin protein expression by using immunoblotting method.
Results: LPS caused a decrease in hot plate latency compared to saline-treated group. Decreased RXRα protein expression was associated with increased expression of TLR4, MyD88, phosphorylated TAK1, NF-κB, phosphorylated NF-κB, COX-2, and IL-1β proteins in the tissues of LPS-treated mice. The LPS-induced changes were prevented by bexarotene. DMSO or bexarotene had no effect on the hot plate latency in saline-treated mice.
Conclusions: These findings suggest that decreased activity of TLR4/MyD88/TAK1/NF-κB/COX-2 pathway associated with proinflammatory cytokine expression contributes to the effect of bexarotene to prevent LPS-induced hyperalgesia in mice.
This work was financially supported by Mersin University (2018-1-TP3-2814) and The Scientific and Technological Research Council of Turkey (SBAG-217S235).

INHIBITION OF TLR4/MYD88/TAK1/NF-&#954;B/COX-2 PATHWAY ACTIVATION CONTRIBUTES TO PROTECTIVE EFFECT OF BEXAROTENE, A RXR&#945; AGONIST, AGAINST LIPOPOLYSACCHARIDE-INDUCED INFLAMMATORY HYPERALGESIA

INHIBITION OF TLR4/MYD88/TAK1/NF-&#954;B/COX-2 PATHWAY ACTIVATION CONTRIBUTES TO PROTECTIVE EFFECT OF BEXAROTENE, A RXR&#945; AGONIST, AGAINST LIPOPOLYSACCHARIDE-INDUCED INFLAMMATORY HYPERALGESIA

INHIBITION OF TLR4/MYD88/TAK1/NF-κB/COX-2 PATHWAY ACTIVATION CONTRIBUTES TO PROTECTIVE EFFECT OF BEXAROTENE, A RXRα AGONIST, AGAINST LIPOPOLYSACCHARIDE-INDUCED INFLAMMATORY HYPERALGESIA