Fcγ Receptor I-Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis
Fcγ Receptor I-Coupled Signaling in Peripheral Nociceptors Mediates Joint Pain in a Rat Model of Rheumatoid Arthritis
复制标题
外周伤害感受器中的 Fc γ 受体 I 偶联信号介导类风湿性关节炎大鼠模型的关节疼痛
DOI：
10.1002/art.41386
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发表时间：
2020-09-06
影响因子：
13.3
通讯作者：
Ma, Chao
中科院分区：
文献类型：
--
作者：
Liu, Fan;Shen, Xinhua;Ma, Chao
目的类风湿关节炎（RA）常伴有关节疼痛和炎症。先前的研究表明，功能性Fc γ受体I （Fc γ RI）在背根神经节（DRG）神经元中表达，可能与抗原诱导关节炎（AIA）啮齿动物模型的疼痛有关。本研究旨在阐明痛觉神经元Fc γ i偶联信号在AIA关节疼痛发展中的作用。方法采用RNA测序方法研究AIA大鼠模型DRG转录组谱的变化。通过将携带loxp - flankedfcgr1a的大鼠与aPirt-specificCreline杂交，建立了原发性感觉神经元特异性fcgr1条件敲除（CKO）大鼠。通过行为学、形态学和分子研究来评估野生型（WT）和CKO大鼠在AIA后的差异。我们首先发现AIA诱导DRG的转录组谱变化，涉及Fc γ ri相关信号通路下游的一些关键蛋白。与WT大鼠相比，CKO大鼠IgG免疫复合物引起的急性疼痛和aia引起的疼痛均有所减轻。此外，在CKO大鼠中，aia诱导的DRGs中Fc γ ri相关信号的激活显著降低。此外，CKO大鼠在AIA后关节肿胀减轻。结论DRG神经元Fc γ i偶联信号的激活在AIA关节疼痛的发生发展中起重要作用。我们的发现可能为病理状态下周围神经系统和免疫系统之间的相互作用提供了新的见解，并可能为治疗RA疼痛提供潜在的生物靶点。
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.