Fcγ Receptor I–Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis
- 8 June 2020
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatology
- Vol. 72 (10), 1668-1678
- https://doi.org/10.1002/art.41386
Abstract
Objective Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies demonstrated that functional FcγRI was expressed in dorsal root ganglion neurons, and might contribute to pain in rodent models of antigen‐induced arthritis (AIA). This study was performed to elucidate the roles of nociceptive neuronal FcγRI‐coupled signaling in the development of joint pain in AIA. Methods RNA sequencing was used to investigate the transcriptome profile changes in the dorsal root ganglion (DRG) in a rat model of AIA. A primary sensory neuron‐specific Fcgr1a conditional knockout (CKO) rat was established by crossing rats carrying a loxP ‐flanked Fcgr1a with a Pirt ‐specific Cre line. Behavioral, morphological and molecular studies were conducted to evaluate the differences between wild‐type and CKO rats after AIA. Results We first showed that AIA induced a transcriptome profile change in the DRG, involving a number of key proteins downstream of the FcγRI‐related signaling pathway. Compared to the wild‐type rats, both the IgG‐immune complex‐induced acute pain and AIA‐induced pain were alleviated in CKO rats. Moreover, the AIA‐induced activation of FcγRI‐related signaling in DRGs was significantly reduced in CKO rats. In addition, CKO rats showed attenuated joint swelling after AIA. Conclusion These results indicate that activation of FcγRI‐coupled signaling in DRG neurons plays an important role in the development of joint pain in AIA. Our findings may provide novel insights into the interactions between the peripheral nervous system and the immune system in pathological conditions, and might suggest potential biotargets for the treatment of pain in RA.Keywords
Funding Information
- National Natural Science Foundation of China (#81771205 (Chao Ma), #81801114 (Fan Liu), #91632113 (Chao Ma))
- China Postdoctoral Science Foundation (#2018M631389 (Fan Liu))
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