Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou.
Department of Anesthesiology, Longgang District Central Hospital of Shenzhen, Shenzhen, Guangdong, China.
Neuroreport. 2023 Oct 4;34(14):713-719. doi: 10.1097/WNR.0000000000001947. Epub 2023 Aug 8.
Paclitaxel is an extensively used chemotherapy antitumor drug and paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common side effect. Rapamycin, originally used as an adjuvant drug for chemotherapy, has recently been found to possess potential neuroprotective activities. Our purposes of this study are to verify the effect of rapamycin on PIPN, which contributes to a new target for PIPN treatment. Mice were given paclitaxel or rapamycin with different injection methods. Paw withdrawal threshold was tested at different time points for mechanical sensitivity assessment. Administration of paclitaxel, both 2 mg/kg and 5 mg/kg, could induce mechanical hypersensitivity. 0.01 mg intrathecal injection of rapamycin showed the best effect on attenuate the mechanical hyperalgesia of PIPN. Intrathecal injection of only rapamycin would not induce the mechanical hyperalgesia while when rapamycin and paclitaxel were used together the mechanical hyperalgesia induced by paclitaxel could be attenuated. Paclitaxel could induce mechanical hyperalgesia in mice and rapamycin could attenuate such mechanical hyperalgesia of PIPN.
紫杉醇是一种广泛应用于化疗的抗肿瘤药物，紫杉醇诱导的周围神经病变（PIPN）是最常见的副作用之一。雷帕霉素最初被用作化疗的辅助药物，最近发现它具有潜在的神经保护活性。我们这项研究的目的是验证雷帕霉素对 PIPN 的作用，为 PIPN 的治疗提供新的靶点。我们用不同的注射方法给小鼠注射紫杉醇或雷帕霉素。在不同时间点测试爪退缩阈值，以评估机械敏感性。注射 2mg/kg 和 5mg/kg 的紫杉醇均可诱导机械性敏感性增加。鞘内注射 0.01mg 的雷帕霉素对减轻 PIPN 的机械性痛觉过敏效果最好。鞘内注射雷帕霉素本身不会引起机械性痛觉过敏，而当雷帕霉素和紫杉醇一起使用时，紫杉醇引起的机械性痛觉过敏可以被减轻。紫杉醇可诱导小鼠产生机械性痛觉过敏，雷帕霉素可减轻 PIPN 的这种机械性痛觉过敏。
