Fcγ Receptor I-Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis

Objective Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies have demonstrated that functional Fc gamma receptor I (Fc gamma RI) is expressed in dorsal root ganglion (DRG) neurons and might contribute to pain in rodent models of antigen-induced arthritis (AIA). This study was undertaken to elucidate the roles of nociceptive neuronal Fc gamma RI-coupled signaling in the development of joint pain in AIA. Methods RNA sequencing was used to investigate the transcriptome profile changes in the DRG in a rat model of AIA. A primary sensory neuron-specificFcgr1aconditional-knockout (CKO) rat was established by crossing rats carrying a loxP-flankedFcgr1awith aPirt-specificCreline. Behavioral, morphologic, and molecular studies were conducted to evaluate the differences between wild-type (WT) 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 Fc gamma RI-related signaling pathway. Compared to the WT rats, both the IgG immune complex-induced acute pain and AIA-induced pain were alleviated in CKO rats. Moreover, the AIA-induced activation of Fc gamma RI-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 Fc gamma RI-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 pathologic conditions and might suggest potential biotargets for the treatment of pain in RA.