Department of Anesthesiology and Pain Research Center, Affiliated Hospital of Jiaxing University & The First Hospital of Jiaxing, Jiaxing, China.
Department of Anesthesiology and Pain Research Center, Affiliated Hospital of Jiaxing University & The First Hospital of Jiaxing, Jiaxing, China.
Eur J Pharmacol. 2021 Oct 15;909:174412. doi: 10.1016/j.ejphar.2021.174412. Epub 2021 Aug 8.
Due to the efficacy and tolerability of the available drugs, the current treatment for cancer-induced bone pain (CIBP) is not considered ideal, and new drugs are required for better treatment results. This study investigated whether intrathecal injection of sulforaphane (SFN) can modulates the noxious behavior associated with CIBP and enhances the analgesic effects of morphine and the possible mechanisms related to these effects were investigated. Walker256 breast cancer cells were injected into the bone marrow cavity of rats to establish the CIBP model. When CIBP rats began to exhibit painful behavior (CIBP 6 days), SFN was injected intrathecally for 7 days. The results showed that SFN alleviated the painful behavioral hypersensitivity caused by cancer, accompanied by nuclear factor, erythroid 2 like 2 (Nrf2), Haem oxygenase 1 (HO-1) activation, nuclear factor kappa B (NF-κB) inhibition and inflammation-related factors (tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-β), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) reduction. In addition, SFN treatment inhibited the proliferation of Walker 256 cells in a dose-dependent manner, promoted mu-opioid receptor (MOR) expression in SH-SY5Y cells and enhanced the antihyperalgesic effects of morphine on CIBP rats by restoring the downregulation of MOR expression in the spinal cord. Interestingly, the antihyperalgesic effects of SFN were partially blocked by opioid receptor antagonists. This study showed that SFN combined with morphine might be a new way to treat CIBP.
由于现有药物的疗效和耐受性，目前癌症相关性骨痛（CIBP）的治疗并不理想，需要新的药物来获得更好的治疗效果。本研究旨在探讨鞘内注射萝卜硫素（SFN）是否能调节与 CIBP 相关的有害行为，并增强吗啡的镇痛效果，并探讨相关机制。将 Walker256 乳腺癌细胞注射到大鼠骨髓腔中建立 CIBP 模型。当 CIBP 大鼠开始出现疼痛行为（CIBP 第 6 天）时，鞘内注射 SFN 持续 7 天。结果表明，SFN 缓解了癌症引起的痛觉行为过敏，同时激活核因子，红系 2 样 2（Nrf2）、血红素加氧酶 1（HO-1），抑制核因子 kappa B（NF-κB）和炎症相关因子（肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和诱导型一氧化氮合酶（iNOS）减少。此外，SFN 处理呈剂量依赖性抑制 Walker256 细胞的增殖，促进 SH-SY5Y 细胞中 μ-阿片受体（MOR）的表达，并通过恢复脊髓中 MOR 表达的下调增强吗啡对 CIBP 大鼠的抗痛觉过敏作用。有趣的是，SFN 的抗痛觉过敏作用部分被阿片受体拮抗剂阻断。本研究表明，SFN 联合吗啡可能是治疗 CIBP 的一种新方法。
