National Human Brain Bank for Development and Function, Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, P. R. China.
Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, P. R. China.
Adv Sci (Weinh). 2023 Apr;10(10):e2205397. doi: 10.1002/advs.202205397. Epub 2023 Feb 2.
Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc-gamma-receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen-specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI-related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI-related signaling in the DRG, and conditional knockout (CKO) of the FcγRI-encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C-reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI-related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI-related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain.
神经病理性疼痛在临床实践中难以治疗，其潜在机制尚未充分阐明。先前的研究表明，背根神经节 (DRG) 中的神经元 Fc-γ 受体 I 型 (FcγRI) 介导抗原特异性疼痛。然而，神经元 FcγRI 在神经病理性疼痛中的机制仍有待探索。在这里，发现在原代神经元中激活 FcγRI 相关信号会在大鼠模型中引起神经病理性疼痛。这项工作首次揭示了坐骨神经损伤会持续激活 DRG 中的神经元 FcγRI 相关信号，并且在大鼠 DRG 神经元中条件敲除 (CKO) FcγRI 编码基因 Fcgr1 可显著减轻神经损伤后的神经病理性疼痛。神经损伤后 DRG 中的 C 反应蛋白 (CRP) 增加，DRG 的 CRP 蛋白通过激活神经元 FcγRI 相关信号引发疼痛。此外，将幼稚 IgG 微注射到 DRG 中可通过抑制神经元 FcγRI 的激活来缓解神经病理性疼痛。这些结果表明，神经元 CRP/FcγRI 相关信号的激活在慢性缩窄性损伤 (CCI) 大鼠神经病理性疼痛的发展中起重要作用。这些发现可能为外周神经损伤后的神经免疫反应提供新的见解，并为神经病理性疼痛提供潜在的治疗靶点。
