Effect of toad skin extracts on the pain behavior of cancer model mice and its peripheral mechanism of action
Effect of toad skin extracts on the pain behavior of cancer model mice and its peripheral mechanism of action
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蟾皮提取物对癌症模型小鼠疼痛行为的影响及其外周作用机制
DOI：
10.1016/j.intimp.2016.11.026
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发表时间：
2017-01-01
影响因子：
5.6
通讯作者：
Xie, Bo
中科院分区：
文献类型：
--
作者：
Chen, Tao;Yuan, Shen-jun;Xie, Bo
研究了爪部癌症疼痛模型小鼠热痛觉过敏和机械痛觉过敏的变化以及蟾皮提取物（TSE）的作用机制。80只雌性小鼠右后爪皮下注射生理盐水或接种H22肝癌细胞，并分别给予生理盐水、溶媒、吗啡和TSE。在治疗前以及首次给药后0.5、1.0、1.5、3和6小时记录疼痛行为，之后在给药后的第2、4、6和8天也进行记录。最后一天，在安乐死后采集样本，用于检测血清和肿瘤组织中的β - 内啡肽（β - END）、促肾上腺皮质激素释放因子（CRF）、白细胞介素 - 1β（IL - 1β）、阿黑皮素原（POMC）、μ - 阿片受体（μ - OR）、CD3 +、CD8 +和CD4 +。结果表明，TSE显著提高了热痛和机械痛的阈值，上调了β - END、CRF、POMC、CD3 +、CD8 +和μ - OR的表达，并下调了CD4 +的表达。这些结果表明，TSE显著缓解了癌症疼痛模型小鼠的疼痛并提高了它们的痛阈。此外，TSE似乎在促进肿瘤浸润淋巴细胞（TILs，CD3 +和CD8 + T细胞）的活性方面发挥着重要作用，并且这种源自免疫细胞的外周镇痛途径可能具有广泛的临床应用潜力。（C）2016爱思唯尔有限公司。保留所有权利。
The changes in thermal and mechanical hyperalgesia in paw cancer pain model mice and the action mechanism of toad skin extracts (TSE) was investigated. Eighty female mice were subcutaneously injected with saline or inoculated with H22 hepatoma cells in the right hind paw and administration with saline, vehicle, morphine and TSE. The pain behavior was recorded before treatment and at 0.5, 1.0, 1.5, 3 and 6 h after initial administration, and thereafter on the 2nd, 4th, 6th, and 8th day after administration. On the last day, samples were collected after the euthanasia for the detection of beta-END, CRF, IL-1 beta, POMC, mu-OR, CD3+, CD8+ and CD4+ in sera and the tumor tissues. The results showed that TSE significantly increased the thresholds of thermal pain and mechanical pain, and upregulated the expressions of beta-END, CRF, POMC, CD3+, CD8+ and mu-OR, and downregulated the expression of CD4+. These results indicate that TSE significantly relieved pain in cancer pain model mice and raised their pain threshold. In addition, TSE seems to play a prominent role in promoting the activity of tumor infiltrating lymphocytes (TILs, CD3+ and CD8+ T cells), and this immune-cell-derived peripheral analgesic pathway might have widespread potential for clinical use. (C) 2016 Elsevier B.V. All rights reserved.