Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis

Abstract

Abstract: Objective To explore the mechanism of peripheral neurons FcγRⅠ regulating pain caused by rheumatoid arthritis. Methods Rheumatoid arthritis models were established in 14 wild-type SD rats and 7 Fcgr1 conditional knockout rats. Wild-type rat control group (control group), rheumatoid arthritis group of wild-type rat (RA group) and rheumatoid arthritis group of Fcgr1 conditional knockout rat (RA+CKO group) were established. Pain behavior was used to detect the changes of mechanical pain threshold and thermal pain threshold 3 and 1 days before modeling and 3, 5, 7 and 9 days after modeling. The expression of Fcgr1 mRNA in dorsal root ganglion (DRG) of Fcgr1 conditional knockout rat was detected by fluorescence in situ hybridization. Immunofluorescence staining was used to detect the changes of IL-1β and IL-18 expression in the DRG and activation of glial cells in the spinal dorsal horn (SDH). Results Compared with the control group, the threshold of mechanical and thermal pain in RA group and (RA+CKO) group were decreased (P＜0.05), the mechanical and thermal pain thresholds of the (RA+CKO) group were significantly higher than of RA group(P＜0.05). Compared with the RA group, the expression of pNF-κB, NLRP3, IL-1β and IL-18 and the protein level of GFAP and Iba1 in the SDH of (RA+CKO) rats were significantly decreased (P＜0.05). Conclusions FcγRⅠ of DRG neurons may promote the synthesis and release of inflammatory cytokines IL-1β and IL-18 through NF-κB/NLRP3 pathway, and cause glial cells activation in the SDH, which may play a role in the mechanism causing pain of rheumatoid arthritis.

Key words: rheumatoid arthritis, pain, central sensitization, Fc-gamma receptor I (FcγRⅠ), immune complex

CLC Number:

R322.8

LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao. Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis[J]. Basic & Clinical Medicine, 2021, 41(7): 963-969.

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