Trigeminal neuralgia (TN) is a type of chronic orofacial pain evoked by trivial stimuli that manifests as episodes of excruciating and sudden, recurrent paroxysmal pain. Most patients are refractory to pharmacological therapy used for the treatment of TN. Mononuclear cells (MNC) and mesenchymal stem/stromal cells (MSC) have shown therapeutic potential in painful neuropathies, but their mechanism of action is not fully understood. The present work aimed to investigate the antinociceptive effect and mechanism of action of MNC and MSC in experimental TN. Mice submitted to the chronic constriction injury of the infraorbital nerve (CCI-ION) mouse model of TN received a single intravenous injection of saline, MNC, or MSC (1 × 10 cells/mouse). The effect of the treatments on the behavioral signs of painful neuropathy, morphological aspects of the infraorbital nerve, and inflammatory and oxidative stress markers in the infraorbital nerve were assessed. MNC and MSC improved behavioral painful neuropathy, activated key cell signaling antioxidant pathways by increasing Nrf2 expression, and reduced the proinflammatory cytokines IL-1β and TNF-α. However, treatment with MSC, but not MNC, was associated with a sustained increase of IL-10 and with the re-establishment of the morphometric pattern of the infraorbital nerve, indicating a difference in the mechanism of action between MNC and MSC. In line with this result, in IL-10 knockout mice, MSC transplantation did not induce an antinociceptive effect. Importantly, these data suggest an IL-10-induced disease-modifying profile related to MSC treatment and reinforce cell therapy's potential in treating trigeminal neuralgia.

中文翻译：

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不同机制指导骨髓单核细胞和骨髓间充质干/基质细胞在三叉神经痛中的抗伤害作用


三叉神经痛 (TN) 是一种由微不足道的刺激引起的慢性口面部疼痛，表现为一阵阵难以忍受的突然、反复发作的阵发性疼痛。大多数患者对用于治疗 TN 的药物治疗无效。单核细胞（MNC）和间充质干细胞/基质细胞（MSC）已显示出治疗疼痛性神经病的潜力，但其作用机制尚不完全清楚。本工作旨在探讨 MNC 和 MSC 在实验性 TN 中的抗伤害作用及其作用机制。患有 TN 眶下神经慢性缩窄损伤 (CCI-ION) 小鼠模型的小鼠接受单次静脉注射盐水、MNC 或 MSC（1 × 10 个细胞/小鼠）。评估了治疗对疼痛性神经病行为体征、眶下神经形态学以及眶下神经炎症和氧化应激标志物的影响。 MNC 和 MSC 改善了行为性疼痛性神经病变，通过增加 Nrf2 表达激活关键细胞信号抗氧化途径，并减少促炎细胞因子 IL-1β 和 TNF-α。然而，MSC（而不是 MNC）治疗与 IL-10 的持续增加以及眶下神经形态模式的重建相关，表明 MNC 和 MSC 之间的作用机制存在差异。与这一结果一致，在 IL-10 敲除小鼠中，MSC 移植没有诱导抗伤害作用。重要的是，这些数据表明 IL-10 诱导的疾病缓解与 MSC 治疗相关，并增强了细胞疗法治疗三叉神经痛的潜力。