Tumor Center, The First Hospital of Jilin University, Changchun, Jilin, China and Department of Gerontology, The First Hospital of Jilin University, Changchun, Jilin, China, Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
Physiol Res. 2019 Jun 30;68(3):501-510. doi: 10.33549/physiolres.934084. Epub 2019 Mar 22.
One of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy for several types of cancers. Our recent study showed that impairment of Nrf2-antioxidant response element (Nrf2-ARE) and upregulation of oxidative signals in the dorsal root ganglion (DRG) of rats with treatment of paclitaxel result in neuropathic pain. The purpose of this study was to examine the beneficial role played by electroacupuncture (EA) in modifying neuropathic pain evoked by paclitaxel via Nrf2-ARE and oxidative mechanisms. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western Blot analysis and ELISA were used to examine expression of Nrf2-ARE and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG. Our data showed that paclitaxel increased mechanical and thermal sensitivity and this was accompanied with impaired Nrf2-ARE and SOD in the DRG and amplified products of oxidative stress (i.e. 8-isoprostaglandin F2alpha and 8-hydroxy-2'-deoxyguanosine). EA treatment largely restored the levels of Nrf2-ARE/SOD and inhibited products of oxidative stress and thereby attenuated mechanical and thermal hypersensitivity induced by paclitaxel. In conclusion, we revealed specific signaling pathways leading to paclitaxel-evoked neuropathic pain, including impairment of Nrf2-ARE and heightened oxidative signals. We further provided evidence for the role of EA in alleviating paclitaxel-neuropathic pain via these molecular mediators.
紫杉醇治疗多种癌症时，其一个显著的限制并发症是疼痛性周围神经病变。我们最近的研究表明，紫杉醇治疗大鼠背根神经节（DRG）中 Nrf2-抗氧化反应元件（Nrf2-ARE）的损伤和氧化信号的上调导致神经病理性疼痛。本研究的目的是通过 Nrf2-ARE 和氧化机制，研究电针（EA）在修饰紫杉醇引起的神经病理性疼痛中的有益作用。通过行为测试来确定大鼠的机械和热敏敏感性。Western Blot 分析和 ELISA 用于检测 Nrf2-ARE 和超氧化物歧化酶（SOD）的表达；以及 DRG 中氧化应激产物的水平。我们的数据表明，紫杉醇增加了机械和热敏敏感性，这伴随着 DRG 中 Nrf2-ARE 和 SOD 的损伤以及氧化应激产物（即 8-异前列腺素 F2alpha 和 8-羟基-2'-脱氧鸟苷）的放大。EA 治疗在很大程度上恢复了 Nrf2-ARE/SOD 的水平，并抑制了氧化应激产物，从而减轻了紫杉醇引起的机械和热敏性过度敏感。总之，我们揭示了导致紫杉醇引起的神经病理性疼痛的特定信号通路，包括 Nrf2-ARE 的损伤和氧化信号的增强。我们进一步提供了证据，证明 EA 通过这些分子介质在缓解紫杉醇性神经病理性疼痛中的作用。
