MicroRNA-143-3p contributes to the regulation of pain responses in collagen-induced arthritis

Abstract

Patients with rheumatoid arthritis (RA) suffer from pain, which is associated with inflammation, peripheral and central pain processing, and joint structure damage. The aim of the present study was to investigate a key microRNA (miR) and its target genes that are involved in the pain responses of RA, and to clarify the mechanism of pain regulation. Collagen-induced arthritis (CIA) was induced in DBA/1 and C57BL/6 mice. The paw swelling, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and expression levels of tumor necrosis factor (TNF)-a and prostaglandin (PG)E 2 in the sera were investigated. Decreased MWT and TWL, and increased TNF-a and PGE 2 , in the CIA model group were observed in DBA/1 and C57BL/6 mice. DBA/1 mice exhibited greater hyperalgesia and higher levels of inflammatory mediators. miR-143-3p expression in the blood and the dorsal root ganglion (DRG) were detected, and low miR-143-3p expression was demonstrated in the blood and DRG tissue of CIA mice. The target genes of miR-143 were predicted and analyzed. A total of 1,305 genes were predicted and 55 pain-associated genes were obtained. Prostaglandin-endoperoxide synthase 2 (Ptgs2), MAS related GPR family member E (Mrgpre), prostaglandin D2 receptor and Tnf were selected as target genes of miR-143. DRG cells were cultured and transfected with miR-143-3p inhibitor or mimic. The expression of Mrgpre, Ptgs2 and Tnf was significantly inhibited following miR-143-3p mimic transfection