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白细胞介素-6(IL-6)/Piezo2 对三叉神经病理性疼痛的影响。

The effect of IL-6/Piezo2 on the trigeminal neuropathic pain.

机构信息

Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao 266000, China.

Department of Neurosurgery, XinHua Hospital, The Cranial Nerve Disease Center of Shanghai, Shanghai JiaoTong University School of Medicine, Shanghai 200092, China.

出版信息

Aging (Albany NY). 2021 Apr 23;13(10):13615-13625. doi: 10.18632/aging.202887.

Abstract

The nature of trigeminal neuropathic pain (TN) attacks is regarded as the ignition of ectopic action potentials from the trigeminal root following vascular compression, which seemed to be related to transmembrane proteins and inflammation factors. This study focused on the mechanosensitive channel Piezo2 and cytokine IL-6. The chronic constriction injury of infraorbital nerve in SD rats was used to establish the TN model. The trigeminal ganglion was then achieved to perform immunocytochemistry studies. A significant upregulation of Piezo2 and IL-6 was showed in the TN model rats. The Piezo2 positive accounted for 72.3±9.5% in those IL-6 positive neurons. The Piezo2 co-localized with CGRP, IB4 and NF-200 but not with GFAP, which implied that it was expressed in both the C-type and the A-type neurons. After administration of GsMTx4 or anti-rat IL-6 antibody in the TN model, the dynamic allodynia and pinprick hyperalgesia scores as well as the mechanical threshold changed significantly. In the sham-operation rates, with local administration of IL-6, an upregulation of Piezo2 was also exhibited. Our study demonstrated that the up-regulation of Piezo2 in the pain afferent neurons following trigeminal nerve injury may play a role in the development of the neuralgia. Meanwhile, the expression of Piezo2 may be modulated by inflammatory cytokines, such as IL-6.

摘要

三叉神经病理性疼痛 (TN) 发作的性质被认为是三叉神经根在血管压迫后异位动作电位的触发,这似乎与跨膜蛋白和炎症因子有关。本研究聚焦于机械敏感通道 Piezo2 和细胞因子 IL-6。通过对 SD 大鼠眶下神经慢性缩窄性损伤建立 TN 模型,然后获得三叉神经节进行免疫细胞化学研究。在 TN 模型大鼠中,Piezo2 和 IL-6 显著上调。IL-6 阳性神经元中 Piezo2 阳性的占 72.3±9.5%。Piezo2 与 CGRP、IB4 和 NF-200 共定位,但与 GFAP 不共定位,这表明它表达于 C 型和 A 型神经元中。在 TN 模型中给予 GsMTx4 或抗大鼠 IL-6 抗体后,动态触诱发痛和刺痛痛觉过敏评分以及机械阈值均发生显著变化。在假手术组中,局部给予 IL-6 也会引起 Piezo2 的上调。本研究表明,三叉神经损伤后痛觉传入神经元中 Piezo2 的上调可能在神经痛的发展中起作用。同时,Piezo2 的表达可能受到炎症细胞因子(如 IL-6)的调节。

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