白细胞介素-10 通过抑制 TNF-α/p65 依赖的 DRG 神经元 Nav1.7 上调缓解神经根痛。
IL-10 alleviates radicular pain by inhibiting TNF-α/p65 dependent Nav1.7 up-regulation in DRG neurons of rats.
机构信息
Department of Spine Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China; Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
出版信息
Brain Res. 2022 Sep 15;1791:147997. doi: 10.1016/j.brainres.2022.147997. Epub 2022 Jun 30.
BACKGROUND
Lumbar disc herniation (LDH) may induce radicular pain, the upregulation of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) contributes to radicular pain by generating ectopic discharge of neurons, but the mechanism is unclear. Previously, we reported pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) up-regulated VGSCs in diabetic neuropathy. In this study, we explored the effect of anti-inflammatory cytokine interleukin-10 (IL-10) on radicular pain and the possible mechanisms.
METHODS
Rat model of LDH was induced by implanting autologous nucleus pulposus (NP). Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. IL-10 and TNF-α level in DRG and cerebrospinal fluid (CSF) were assessed by Enzyme-linked immunosorbent assay (ELISA). IL-10 was intrathecally delivered for 12 days. The expression of IL-10R1 and sodium channel Nav1.7 was displayed by immunofluorescence staining. The protein level of TNF-α and p-p65 was measured by western blotting.
RESULTS
NP implantation increased Nav1.7 expression in DRG neurons, decreased IL-10 level and increased TNF-α level in DRG and CSF. IL-10 significantly alleviated pain behaviors of rats with NP. IL-10R1 was co-localized with neurons but not with satellite cells in DRG. IL-10 decreased Nav1.7 and TNF-α/p-p65 expression in DRG of rats with NP. Co-administration of TNF-α with IL-10 counteracted the effect of IL-10 on pain behaviors, Nav1.7 and TNF-α/p-p65 expression of rats with NP.
CONCLUSIONS
The study revealed that IL-10 alleviated radicular pain by inhibiting TNF-α/p-p65 dependent Nav1.7 up-regulation in DRG neurons.
背景
腰椎间盘突出症（LDH）可引起神经根痛，背根神经节（DRG）中电压门控钠通道（VGSCs）的上调通过产生神经元的异位放电导致神经根痛，但机制尚不清楚。先前，我们报道促炎细胞因子肿瘤坏死因子-α（TNF-α）上调糖尿病神经病变中的 VGSCs。在这项研究中，我们探讨了抗炎细胞因子白细胞介素-10（IL-10）对神经根痛的影响及其可能的机制。
方法
通过植入自体髓核（NP）诱导大鼠 LDH 模型。使用 von Frey 纤维和热板试验分别评估机械和热痛阈值。通过酶联免疫吸附试验（ELISA）评估 DRG 和脑脊液（CSF）中的 IL-10 和 TNF-α水平。IL-10 鞘内给药 12 天。通过免疫荧光染色显示 IL-10R1 和钠通道 Nav1.7 的表达。通过 Western blot 测量 TNF-α 和 p-p65 的蛋白水平。
结果
NP 植入增加了 DRG 神经元中 Nav1.7 的表达，降低了 DRG 和 CSF 中的 IL-10 水平，增加了 TNF-α水平。IL-10 显著缓解了 NP 大鼠的疼痛行为。IL-10R1 与 DRG 中的神经元共定位，但与卫星细胞不共定位。IL-10 降低了 NP 大鼠 DRG 中 Nav1.7 和 TNF-α/p-p65 的表达。与 IL-10 共同给予 TNF-α 可拮抗 IL-10 对 NP 大鼠疼痛行为、Nav1.7 和 TNF-α/p-p65 表达的影响。
结论
该研究表明，IL-10 通过抑制 DRG 神经元中 TNF-α/p-p65 依赖性 Nav1.7 上调缓解神经根痛。
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