Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Front Immunol. 2022 Jun 27;13:889286. doi: 10.3389/fimmu.2022.889286. eCollection 2022.
Persistent arthritis pain after resolution of joint inflammation represents a huge health burden in patients with rheumatoid arthritis (RA). However, the underling mechanisms are poorly understood. We and other groups recently revealed that FcγRI, a key immune receptor, is functionally expressed in joint nociceptors. Thus, we investigated a potential role of sensory neuron expressed FcγRI in postinflammatory arthritis pain in a mouse model of collagen antibody-induced arthritis (CAIA). Here, we show that global deletion of significantly attenuated mechanical hyperalgesia in the ankle and hind paw of female mice in both inflammatory and postinflammatory phases of CAIA. No obvious differences in cartilage destruction were observed after resolution of joint inflammation between genotypes. hybridization (ISH) revealed that a larger proportion of dorsal root ganglion (DRG) neurons expressed mRNA signal in the late phase of CAIA. Conditional deletion of in primary sensory neurons produced similar analgesic effects without affecting joint swelling. Knockdown of expression within DRG in the postinflammatory phase of CAIA alleviated persistent pain. Inflammation within DRG after resolution of joint inflammation in the CAIA model was evidenced by T cell and neutrophil infiltration and upregulated mRNA expression of numerous inflammatory mediators. Yet, such changes were not altered by genetic deletion of . We suggest that neuroinflammation within the DRG after resolution of joint inflammation might upregulate FcγRI signaling in DRG neurons. Sensory neuron expressed FcγRI thus merits exploration as a potential target for the treatment of arthritis pain that persists in RA patients in remission.
炎症消退后持续性关节炎疼痛是类风湿关节炎（RA）患者的巨大健康负担。然而，其潜在机制尚不清楚。我们和其他研究组最近发现，FcγRI（一种关键的免疫受体）在关节伤害感受器中具有功能性表达。因此，我们在胶原抗体诱导关节炎（CAIA）的小鼠模型中研究了感觉神经元表达的 FcγRI 在炎症后关节炎疼痛中的潜在作用。结果显示，在 CAIA 的炎症和炎症后阶段， 基因敲除显著减轻了雌性小鼠踝关节和后爪的机械性痛觉过敏。在关节炎症消退后，两种基因型之间的软骨破坏没有明显差异。杂交（ISH）显示，在 CAIA 的后期，更大比例的背根神经节（DRG）神经元表达 mRNA 信号。在初级感觉神经元中条件性敲除 产生了类似的镇痛效果，而不影响关节肿胀。在 CAIA 的炎症后阶段，DRG 内的 表达下调缓解了持续性疼痛。CAIA 模型中关节炎症消退后，DRG 内的炎症表现为 T 细胞和中性粒细胞浸润以及许多炎症介质的 mRNA 表达上调。然而，这种变化不受 基因敲除的影响。我们认为，DRG 内的炎症消退后的神经炎症可能上调了 DRG 神经元中的 FcγRI 信号。因此，感觉神经元表达的 FcγRI 可能值得作为治疗缓解期 RA 患者持续性关节炎疼痛的潜在靶点进行探索。
