Sulforaphane alleviates hyperalgesia and enhances analgesic potency of morphine in rats with cancer-induced bone pain.
Sulforaphane alleviates hyperalgesia and enhances analgesic potency of morphine in rats with cancer-induced bone pain.
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萝卜硫素可减轻癌症引起的骨痛大鼠的痛觉过敏并增强吗啡的镇痛效力。
DOI：
10.1016/j.ejphar.2021.174412
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发表时间：
2021
影响因子：
5
通讯作者：
M. Yao
中科院分区：
文献类型：
--
作者：
Jie Fu;Miao Xu;Longsheng Xu;H. Ni;Baoxia Zhao;Chaobo Ni;Mingde Huang;Jianjun Zhu;G. Luo;M. Yao
由于现有药物的疗效和耐受性，目前治疗癌症骨痛(CIBP)的方法并不理想，需要新药才能获得更好的治疗效果。本研究观察鞘内注射萝卜硫醚(SFN)能否调节CIBP的致痛行为，增强吗啡的镇痛作用，并探讨其可能机制。将Walker256乳腺癌细胞注入大鼠骨髓腔内建立CIBP模型。当CIBP大鼠出现疼痛行为时(CIBP 6天)，鞘内注射SFN 7天。结果表明，三七总皂苷可减轻癌症所致的痛性行为过敏，并伴有核因子、红系2型(NRF2)、血红素氧合酶1(HO-1)激活、核因子-kappaB(NF-κB)抑制和炎症相关因子(肿瘤坏死因子-α(α-α)、白介素1-β(IL-β)、白介素6(IL-6)、诱导型一氧化氮合酶(INOS)降低)。此外，SFN还能剂量依赖性地抑制Walker 256细胞的增殖，促进SH-SY5Y细胞内Mu阿片受体(Mor)的表达，并通过恢复脊髓Mor表达的下调来增强吗啡对CIBP大鼠的止痛作用。有趣的是，SFN的止痛作用可被阿片受体拮抗剂部分阻断。提示三七神经核联合吗啡治疗CIBP可能是一种新的治疗方法。
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.