Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons
Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons
复制标题
电针通过抑制感觉神经元中的 TLR4 信号传导和 TRPV1 上调减轻紫杉醇引起的大鼠周围神经病理性疼痛
DOI：
10.3390/ijms20235917
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Liu, Boyi
中科院分区：
文献类型：
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作者：
Li, Yuanyuan;Yin, Chengyu;Liu, Boyi
紫杉醇诱导的周围神经病变是紫杉醇治疗期间的常见不良反应，导致化疗期间和癌症幸存者的感觉异常和神经性疼痛。常规治疗通常无效，并具有不良反应。本研究旨在探讨电针对紫杉醇诱导的神经病理性疼痛大鼠模型的影响及其相关机制。电针能显著持续地减轻紫杉醇引起的疼痛超敏反应。机制上，TLR 4（Toll样受体4）和下游信号转导MyD 88（髓样分化初级反应88）和TRPV 1（瞬时受体电位Vallinoid 1）上调背根神经节（DRG）紫杉醇治疗的大鼠，而EA减少他们的过度表达。Ca ~（2+）显像进一步显示，紫杉醇处理的大鼠DRG神经元TRPV_1通道活性增强，而EA抑制TRPV_1通道活性增强。TRPV 1的药理学阻断模拟了EA对疼痛超敏反应的镇痛作用，而辣椒素则逆转了EA的作用。脊髓星形胶质细胞和小胶质细胞在紫杉醇治疗的大鼠被激活，而EA减少激活。这些结果表明，EA通过可能涉及抑制DRG神经元中的TLR 4信号传导和TRPV 1上调的机制减轻紫杉醇诱导的周围神经病理性疼痛，这进一步导致脊髓胶质细胞活化减少。我们的工作支持EA作为紫杉醇诱导的神经病理性疼痛的潜在替代疗法。
Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca2+ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA’s effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain.