Effect of peripheral endothelin-1 concentration on carcinoma-induced pain in mice
Effect of peripheral endothelin-1 concentration on carcinoma-induced pain in mice
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DOI：
10.1016/j.ejpain.2007.06.001
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Schmidt, Brian L.
中科院分区：
文献类型：
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作者：
Pickering, Victoria;Gupta, R. Jay;Schmidt, Brian L.
在这项研究中，我们研究了外周血内皮素-1(ET-1)浓度在癌痛模型中的作用。为了验证肿瘤微环境中ET-1的浓度在决定癌痛程度中的重要作用这一假设，我们使用了两种在ET-1产生方面存在显着差异的癌痛小鼠模型。这两种小鼠癌症模型是通过将来自人类口腔鳞状细胞癌(SCC)和黑色素瘤的细胞注射到雌性小鼠的后爪中而产生的。SCC组的疼痛明显大于黑色素瘤组，这表明疼痛由对机械刺激的反应的戒断阈值的降低而指示。鳞癌组外周血中ET-1浓度明显高于癌微环境组。与黑色素瘤模型相比，鳞癌模型瘤内ET-1mRNA和ET-1蛋白的表达显著升高。ET受体拮抗剂仅在鳞状细胞癌模型中作为癌痛的止痛剂。为了解决肿瘤体积的潜在混杂因素，我们在两个模型中评估了肿瘤体积对癌痛的贡献。黑色素瘤组肿瘤平均体积明显大于鳞癌组。在两组中，疼痛程度与肿瘤体积相关，但在黑色素瘤组这种相关性更强。我们得出结论，在癌症疼痛小鼠模型中，ET-1浓度是疼痛程度的决定因素，在产生癌症疼痛方面，它是比肿瘤体积更重要的因素。这些结果表明，未来针对ET-1受体拮抗剂的癌症疼痛治疗方案是有希望的，并且可能是针对肿瘤类型的。(C)2007年欧洲国际疼痛研究协会分会联合会。爱思唯尔有限公司出版。保留所有权利。
In this study, we investigated the role of the peripheral endothelin-1 (ET-1) concentration in a cancer pain model. To test the hypothesis that the concentration of ET-1 in the tumor microenvironment is important in determining the level of cancer pain we used two cancer pain mouse models that differed significantly in production of ET-1. The two mouse cancer models were produced by injection of cells derived from a human oral squamous cell carcinoma (SCC) and melanoma into the hind paw of female mice. Pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, was significantly greater in the SCC group than the melanoma group. The peripheral concentration of ET-1 within the cancer microenvironment was significantly greater in the SCC group. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly higher in the SCC model compared to the melanoma model. ET receptor antagonism was effective as an analgesic for cancer pain in the SCC model only. To address the potential confounding factor of tumor volume we evaluated the contribution of tumor volume to cancer pain in the two models. The mean volumes of the tumors in the melanoma group were significantly greater than the tumors in the SCC group. In both groups, the pain level correlated with tumor volume, but the correlation was stronger in the melanoma group. We conclude that ET-1 concentration is a determinant of the level of pain in a cancer pain mouse model and it is a more important factor than tumor volume in producing cancer pain. These results suggest that future treatment regimens for cancer pain directed at ET-1 receptor antagonism show promise and may be tumor type specific. (C) 2007 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.