Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Brain Behav Immun. 2017 May;62:351-361. doi: 10.1016/j.bbi.2017.03.001. Epub 2017 Mar 2.
Antigen-specific immune diseases such as rheumatoid arthritis are often accompanied by pain and hyperalgesia. Our previous studies have demonstrated that Fc-gamma-receptor type I (FcγRI) is expressed in a subpopulation of rat dorsal root ganglion (DRG) neurons and can be directly activated by IgG immune complex (IgG-IC). In this study we investigated whether neuronal FcγRI contributes to antigen-specific pain in the naïve and rheumatoid arthritis model rats. In vitro calcium imaging and whole-cell patch clamp recordings in dissociated DRG neurons revealed that only the small-, but not medium- or large-sized DRG neurons responded to IgG-IC. Accordingly, in vivo electrophysiological recordings showed that intradermal injection of IgG-IC into the peripheral receptive field could sensitize only the C- (but not A-) type sensory neurons and evoke action potential discharges. Pain-related behavioral tests showed that intradermal injection of IgG-IC dose-dependently produced mechanical and thermal hyperalgesia in the hindpaw of rats. These behavioral effects could be alleviated by localized administration of non-specific IgG or an FcγRI antibody, but not by mast cell stabilizer or histamine antagonist. In a rat model of antigen-induced arthritis (AIA) produced by methylated bovine serum albumin, FcγRI were found upregulated exclusively in the small-sized DRG neurons. In vitro calcium imaging revealed that significantly more small-sized DRG neurons responded to IgG-IC in the AIA rats, although there was no significant difference between the AIA and control rats in the magnitude of calcium changes in the DRG neurons. Moreover, in vivo electrophysiological recordings showed that C-nociceptive neurons in the AIA rats exhibited a greater incidence of action potential discharges and stronger responses to mechanical stimuli after IgG-IC was injected to the receptive fields. These results suggest that FcγRI expressed in the peripheral nociceptors might be directly activated by IgG-IC and contribute to antigen-specific pain in pathological conditions.
抗原特异性免疫疾病，如类风湿性关节炎，常伴有疼痛和痛觉过敏。我们之前的研究表明，Fc-γ 受体 I 型（FcγRI）在大鼠背根神经节（DRG）神经元的一个亚群中表达，并且可以被 IgG 免疫复合物（IgG-IC）直接激活。在这项研究中，我们研究了神经元 FcγRI 是否有助于在未致敏和类风湿性关节炎模型大鼠中产生抗原特异性疼痛。在分离的 DRG 神经元中的体外钙成像和全细胞膜片钳记录显示，只有小而不是中或大 DRG 神经元对 IgG-IC 有反应。相应地，体内电生理记录显示，将 IgG-IC 皮内注射到外周感受野只能使 C-（而非 A-）型感觉神经元敏化，并引发动作电位放电。与疼痛相关的行为测试表明，皮内注射 IgG-IC 可剂量依赖性地引起大鼠后爪的机械性和热痛觉过敏。这些行为效应可以通过局部给予非特异性 IgG 或 FcγRI 抗体来缓解，但不能通过肥大细胞稳定剂或组胺拮抗剂来缓解。在由甲基化牛血清白蛋白引起的抗原诱导性关节炎（AIA）大鼠模型中，发现 FcγRI 仅在上皮小 DRG 神经元中上调。体外钙成像显示，在 AIA 大鼠中，对 IgG-IC 有反应的小 DRG 神经元明显增多，尽管在 AIA 大鼠和对照组大鼠中，DRG 神经元的钙变化幅度没有明显差异。此外，体内电生理记录显示，在将 IgG-IC 注射到感受野后，AIA 大鼠中的 C-伤害性神经元表现出更高的动作电位放电发生率和对机械刺激的更强反应。这些结果表明，外周伤害感受器中表达的 FcγRI 可能被 IgG-IC 直接激活，并有助于病理状态下的抗原特异性疼痛。
