Salidroside Alleviates Chronic Constriction Injury-Induced Neuropathic Pain and Inhibits of TXNIP/NLRP3 Pathway
Salidroside Alleviates Chronic Constriction Injury-Induced Neuropathic Pain and Inhibits of TXNIP/NLRP3 Pathway
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DOI：
10.1007/s11064-021-03459-y
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发表时间：
2021-10-09
影响因子：
4.4
通讯作者：
Yang, Fei
中科院分区：
文献类型：
--
作者：
Hu, Tingting;Sun, Qingyu;Yang, Fei
神经性疼痛是世界范围内最常见的需要治疗的疾病之一。红景天苷（SAL）是从红景天中提取的苯丙素类葡萄糖苷，已被认为对慢性疼痛具有镇痛作用。然而，SAL是否能减轻周围神经损伤后的疼痛敏感性及其作用机制尚不清楚。一些研究表明，脊髓NOD样受体蛋白3（NLRP 3）炎性体及其相关蛋白的激活有助于神经病理性疼痛的发病机制。本研究调查了脊髓NLRP 3炎性体轴在神经病理性疼痛发展中激活的时间过程，以及SAL是否可以通过调节NLRP 3炎性体来有效治疗这种类型的疼痛。在慢性压迫性损伤（CCI）小鼠模型中，脊髓NLRP 3炎性小体相关蛋白和NLRP 3介质TXNIP在损伤后第14天至第28天上调。CCI后TXNIP和NLRP 3炎性小体相关蛋白主要表达于脊髓背角神经元和小胶质细胞。从CCI损伤第7天开始连续14天腹腔注射SAL 200 mg/kg，可改善CCI模型的机械和热过敏性。此外，SAL还能抑制TXNIP/NLRP 3炎性体轴的激活，减轻神经损伤引起的脊髓背角神经元丢失。上述结果表明，SAL对CCI神经病理性疼痛模型具有镇痛和神经保护作用。
Neuropathic pain is one of the most common conditions requiring treatment worldwide. Salidroside (SAL), a phenylpropanoid glucoside extracted from Rhodiola, has been suggested to produce an analgesic effect in chronic pain. However, whether SAL could alleviate pain hypersensitivity after peripheral nerve injury and its mode of action remains unclear. Several studies suggest that activation of the spinal NOD-like receptor protein 3 (NLRP3) inflammasome and its related proteins contribute to neuropathic pain's pathogenesis. This study investigates the time course of activation of spinal NLRP3 inflammasome axis in the development of neuropathic pain and also whether SAL could be an effective treatment for this type of pain by modulating NLRP3 inflammasome. In the chronic constriction injury (CCI) mice model, spinal NLRP3 inflammasome-related proteins and TXNIP, the mediator of NLRP3, were upregulated from the 14th to the 28th day after injury. The TXNIP and NLRP3 inflammasome-related proteins were mainly present in neurons and microglial cells in the spinal dorsal horn after CCI. Intraperitoneal injection of SAL at 200 mg/kg for 14 consecutive days starting from the 7th day of CCI injury could ameliorate mechanical and thermal hypersensitivity in the CCI model. Moreover, SAL inhibited the activation of the TXNIP/NLRP3 inflammasome axis and mitigated the neuronal loss of spinal dorsal horn induced by nerve injury. These results indicate that SAL could produce analgesic and neuroprotective effects in the CCI model of neuropathic pain.