Dong Zhi-Bin, Wang Yu-Jia, Wan Wen-Jun, Wu Ji, Wang Bo-Jun, Zhu Hai-Li, Xie Min, Liu Ling
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
Exp Ther Med. 2022 Jul 21;24(3):586. doi: 10.3892/etm.2022.11523. eCollection 2022 Sep.
Oxaliplatin (OXA) is a common chemotherapy drug and exhibits clinical activity in several cancer types. Its anticancer clinical effect is frequently accompanied by neurotoxicity. The symptoms include paresthesia and pain, which adversely affect the quality of life of patients. In the present study, five consecutive intraperitoneal injections of 4 mg/kg OXA were used to mimic chemotherapy in rats. OXA administration induced mechanical allodynia, activated spinal astrocytes and triggered the inflammatory response. To explore potential therapeutic options for OXA-induced neuropathic pain, resveratrol (Res) was intrathecally injected into the spinal cord of OXA-treated rats. Paw withdrawal threshold values of OXA-treated rats were increased, indicating an antinociception effect of Res on OXA-induced pain. Additionally, Res treatment reduced the levels of glial fibrillary acidic protein, TNF-α, IL-1β and NF-κB, which were upregulated in OXA-treated rats (compared with control). Furthermore, Auto Dock data showed that Res binds to cyclooxygenase-2 (COX-2) through six hydrogen bonds. Western blot analysis and reactive oxygen species (ROS) assays indicated that Res treatment decreased COX-2 expression and suppressed ROS production. In summary, intrathecal injection of Res reduced the spinal COX-2-mediated ROS generation and inflammatory reaction, suppressed astrocytic activation, and alleviated OXA-induced neuropathic pain.
奥沙利铂（OXA）是一种常用的化疗药物，在多种癌症类型中均表现出临床活性。其抗癌临床效果常伴有神经毒性。症状包括感觉异常和疼痛，这对患者的生活质量产生不利影响。在本研究中，连续五次腹腔注射4mg/kg奥沙利铂用于模拟大鼠化疗。给予奥沙利铂可诱导机械性异常性疼痛，激活脊髓星形胶质细胞并引发炎症反应。为了探索奥沙利铂诱导的神经性疼痛的潜在治疗方案，将白藜芦醇（Res）鞘内注射到接受奥沙利铂治疗的大鼠脊髓中。接受奥沙利铂治疗的大鼠的爪部撤离阈值升高，表明白藜芦醇对奥沙利铂诱导的疼痛具有抗伤害感受作用。此外，白藜芦醇治疗降低了胶质纤维酸性蛋白、肿瘤坏死因子-α、白细胞介素-1β和核因子-κB的水平，这些因子在接受奥沙利铂治疗的大鼠中上调（与对照组相比）。此外，自动对接数据显示白藜芦醇通过六个氢键与环氧化酶-2（COX-2）结合。蛋白质免疫印迹分析和活性氧（ROS）检测表明，白藜芦醇治疗降低了COX-2表达并抑制了ROS产生。总之，鞘内注射白藜芦醇减少了脊髓COX-2介导的ROS生成和炎症反应，抑制了星形胶质细胞活化，并减轻了奥沙利铂诱导的神经性疼痛。
