Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice
Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice
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脊髓白细胞介素 33 及其受体 ST2 导致小鼠骨癌引起的疼痛
DOI：
10.1016/j.neuroscience.2013.08.026
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发表时间：
2013-12
期刊：
影响因子：
3.3
通讯作者：
Huimin Chen
中科院分区：
文献类型：
--
作者：
Yanqing Wang;Hui Zhang;Shenbin Liu;Ping Han;Shan Hu;Qi Li;Zhifu Wang;Qiliang Maoying;Huimin Chen
癌症疼痛，特别是骨癌疼痛，影响癌症患者的生活质量，目前的治疗方法有限。白细胞介素（IL）-33是IL-1超家族的新成员，参与炎症性疼痛的调节。然而，研究集中在其在癌症疼痛的调制的作用已经很少。本研究旨在研究脊髓IL-33/ST 2信号转导是否参与了小鼠骨癌诱导的疼痛。通过股内接种4 T1乳腺癌细胞诱导骨癌。接种癌细胞的小鼠表现出机械性异常性疼痛、热痛觉过敏和肢体使用减少，而磷酸盐缓冲盐水或热灭活细胞注射小鼠与未治疗小鼠相比无显著差异。随着时间的推移和骨质破坏，疼痛过敏行为恶化。脊髓组织中IL-33及其相关细胞因子（IL-1β、IL-6、TNF-α）的mRNA和蛋白水平均显著升高。与注射载体的小鼠相比，鞘内施用ST 2抗体以阻断IL-33/ST 2信号传导以剂量依赖性方式减轻骨癌疼痛小鼠的疼痛行为。此外，与野生型小鼠相比，ST 2 −/−小鼠的肢体使用和热痛觉过敏显着改善。与此同时，携带癌症的ST 2 −/−小鼠的脊髓IL-1β、IL-6和TNF-α浓度没有显著变化。这些数据进一步表明，IL-33/ST 2信号在癌症疼痛中起着至关重要的作用。我们的研究结果为IL-33及其受体ST 2可能成为治疗骨癌患者疼痛的潜在治疗靶点提供了证据。
Cancer pain, particularly bone cancer pain, affects the quality of life of cancer patients, and current treatments are limited. Interleukin (IL)-33, a new member of the IL-1 super family, has been reported to be involved in the modulation of inflammatory pain. However, studies focused on its role in the modulation of cancer pain have been rare. The present study was designed to investigate whether spinal IL-33/ST2 signaling was involved in bone cancer-induced pain in mice. Bone cancer was induced via intra-femoral inoculation of 4T1 mammary carcinoma cells. The mice inoculated with carcinoma cells showed mechanical allodynia, heat hyperalgesia and a reduction in limb use, whereas phosphate-buffered saline or heat-killed cells-injected mice showed no significant difference compared to non-treated mice. The pain hypersensitive behaviors worsened over time and with bone destruction. Both the mRNA and the protein levels of IL-33 and relative cytokines (IL-1β, IL-6, TNF-a) were significantly increased in the spinal cord after the inoculation of carcinoma cells. Intrathecal administration of ST2 antibody to block IL-33/ST2 signaling alleviated pain behaviors in a dose-dependent manner in bone cancer pain mice compared with vehicle-injected mice. Moreover, the ST2−/−mice showed a significant amelioration of limb use and heat hyperalgesia compared to wild-type mice. Meanwhile, concentrations of spinal IL-1β, IL-6 and TNF-a in the cancer-bearing ST2−/−mice had no significant changes. These data further suggested that IL-33/ST2 signaling played a vital role in cancer pain. Our results provided evidence that IL-33 and its receptor ST2 may be a potential therapeutic target for the treatment of pain in bone cancer patients.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
影响因子：
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作者：
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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