癌症患者常遭受剧烈疼痛折磨，而现有药物常常不能有效镇痛。德国研究人员日前报告说找到了癌症产生剧痛的原因，有望帮助癌症患者缓解疼痛。
德国海德堡大学药理学研究所16日发表新闻公报说，研究人员在检查实验鼠身上的肿瘤释放哪些信号物质时，发现了两种特殊的分子。通过电极检测，发现癌变组织周围的神经细胞与这些分子接触后变得对压力特别敏感。
现实生活中，癌症患者常常因为碰到肿瘤部位而感到疼痛。肿瘤生长本身也会产生压力，从而引发疼痛。此外，癌细胞似乎也利用这些特殊分子来促进自己的生长。
在进一步的动物实验中，研究人员通过注射抗体蛋白质，封锁了神经细胞与肿瘤释放的信号物质的接触点，结果癌变组织周边神经细胞的敏感性和肿瘤的生长速度都有所下降。
公报说，下一步研究人员将验证在人体肿瘤部位采取类似措施是否也能起到镇痛的效果。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Medicine 7 June 2009 | doi:10.1038/nm.1976
Hematopoietic colony–stimulating factors mediate tumor-nerve interactions and bone cancer pain
Matthias Schweizerhof1, Sebastian St?sser1,6, Martina Kurejova1,6, Christian Njoo1,6, Vijayan Gangadharan1, Nitin Agarwal1, Martin Schmelz2, Kiran Kumar Bali1, Christoph W Michalski1,3,7, Stefan Brugger1,7, Anthony Dickenson4, Donald A Simone5 & Rohini Kuner1
Pain is one of the most severe and debilitating symptoms associated with several forms of cancer1, 2. Various types of carcinomas and sarcomas metastasize to skeletal bones and cause spontaneous bone pain and hyperalgesia, which is accompanied by bone degradation and remodeling of peripheral nerves2. Despite recent advances, the molecular mechanisms underlying the development and maintenance of cancer-evoked pain are not well understood2. Several types of non-hematopoietic tumors secrete hematopoietic colony-stimulating factors that act on myeloid cells3 and tumor cells4. Here we report that receptors and signaling mediators of granulocyte- and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF)3 are also functionally expressed on sensory nerves. GM-CSF sensitized nerves to mechanical stimuli in vitro and in vivo, potentiated CGRP release and caused sprouting of sensory nerve endings in the skin. Interruption of G-CSF and GM-CSF signaling in vivo led to reduced tumor growth and nerve remodeling, and abrogated bone cancer pain. The key significance of GM-CSF signaling in sensory neurons was revealed by an attenuation of tumor-evoked pain following a sensory nerve–specific knockdown of GM-CSF receptors. These results show that G-CSF and GM-CSF are important in tumor-nerve interactions and suggest that their receptors on primary afferent nerve fibers constitute potential therapeutic targets in cancer pain.
1 Pharmacology Institute, University of Heidelberg, Heidelberg, Germany.
2 Department of Anesthesiology and Intensive Care Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
3 Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
4 Department of Pharmacology, University College London, London, UK.
5 Department of Diagnostic & Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota, USA.
6 These authors contributed equally to this work.
7 Present addresses: Surgery Clinic, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany (C.W.M.); Anesthesiology and Intensive Medicine, University Clinic of Basel, Basel, Switzerland (S.B.).
