Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain
Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain
复制标题
脊柱高活动性组框 1 会导致骨癌疼痛大鼠模型中的机械异常性疼痛。
DOI：
10.1016/j.bbrc.2010.04.086
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发表时间：
2010-05-14
影响因子：
3.1
通讯作者：
Li, Yong-Qi
中科院分区：
文献类型：
--
作者：
Tong, Wei;Wang, Wei;Li, Yong-Qi
骨癌引起的疼痛的机制在很大程度上尚不清楚。先前的研究表明，脊髓背角的神经炎症尤其重要。高迁移率族蛋白 1 (HMGB1) 首次被报道为非组蛋白染色体蛋白，现在被认为是炎症介质。我们假设 HMGB1 可以触发脊髓背角细胞因子的释放，并导致骨癌疼痛。为了验证这一假设，我们首先建立了通过胫骨内注射 Walker 256 乳腺癌细胞诱导的骨癌疼痛模型。通过放射学分析监测胫骨的结构损伤。测量机械异常性疼痛并评估脊髓HMGB1和IL-1β的表达。我们观察到，接种癌细胞（而非热灭活细胞）会在接种后 9 天至 21 天期间诱导进行性骨质破坏。行为测试表明，注射癌细胞的大鼠在第9天出现明显的伤害性反应，并且这种机械性异常性疼痛在接种后至少持续21天。接种肿瘤细胞显着增加脊髓背角HMGB1的表达，而鞘内注射HMGB1中和抗体显示出有效且可靠的抗异常疼痛效果，且呈剂量依赖性。癌痛大鼠中 IL-1 β 显着增加，而鞘内注射抗 HMGB1 可以降低 IL-1 β。结合之前的报道，我们预测骨癌会诱导 HMGB1 产生，增强脊髓 IL-1 β 表达，从而调节脊髓兴奋性突触传递和疼痛反应。 (C) 2010 Elsevier Inc. 保留所有权利。
Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1 beta was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1 beta was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1 beta. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1 beta expression and thus modulating spinal excitatory synaptic transmission and pain response. (C) 2010 Elsevier Inc. All rights reserved.