Fan Liu1, Xinhua Shen2, Si Su1, Huan Cui1, Yehong Fang1, Tao Wang1, Lianfeng Zhang3, Yuguang Huang4, Chao Ma1. 1. Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences and Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, China. 2. Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China. 3. Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, and Peking Union Medical College, Beijing, China. 4. Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Peking Union Medical College Hospital, and Chinese Academy of Medical Sciences, Beijing, China.
Abstract
OBJECTIVE: Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies have demonstrated that functional Fcγ receptor I (FcγRI) 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 FcγRI-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-specific Fcgr1a conditional-knockout (CKO) rat was established by crossing rats carrying a loxP-flanked Fcgr1a with a Pirt-specific Cre line. 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 FcγRI-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 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 pathologic conditions and might suggest potential biotargets for the treatment of pain in RA.
OBJECTIVE:Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies have demonstrated that functional Fcγ receptor I (FcγRI) 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 FcγRI-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-specific Fcgr1a conditional-knockout (CKO) rat was established by crossing rats carrying a loxP-flanked Fcgr1a with a Pirt-specific Cre line. 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 FcγRI-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 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 pathologic conditions and might suggest potential biotargets for the treatment of pain in RA.