Neural Mechanisms of Cancer Pain

癌痛的神经机制

• 批准号: 6515035
• 负责人: Donald Simone
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515035
• 关键词: C fiber; cancer pain; cell proliferation; confocal scanning microscopy; disease /disorder model; endothelin; fibrosarcoma; hyperalgesia; immunocytochemistry; laboratory mouse; neoplastic growth; nerve growth factors; neurogenesis; nociceptors; tumor necrosis factor alpha

DESCRIPTION:(from applicant's abstract) Pain resulting from cancer profoundly contributes to the erosion of the patients' quality of life although cancer pain is often managed effectively with narcotics, the many undesirable side effects associated with these medications limit their use. The development of new and effective treatments for cancer pain is hampered by a paucity of knowledge about the basic neurobiological mechanisms underlying cancer pain. We have been involved in the development of an animal model of cancer pain that will allow rigorous exploration of underlying mechanisms and testing of specific hypotheses. In the proposed studies, a multidisciplinary approach using behavioral, electrophysiological and morphological methods will be used to investigate peripheral mechanisms of cancer pain using a newly developed murine model. Our preliminary studies show that tumor growth following subcutaneous implantation of osteolytic fibrosarcoma cells into the hindpaw results in mechanical hyperalgesia on the ipsilateral paw. We will investigate effects of tumor growth on excitability and morphoiogy of cutaneous nociceptors in skin overlying the tumor. In electrophysiological recordings, we will determine whether nociceptors are spontaneously active and exhibit greater responses to natural stimuli (mechanical, heat and cold). In addition, we will determine the role of tumor necrosis factor, endothelin-1 and nerve growth factor each of which are hypothesized to be secreted from the tumor, on tumor-evoked nociception and on excitability of nociceptors. We will also investigate whether the fibrosarcoma tumor increases neural innervation of the epidermis in skin overlying the tumor. Immunostainingand confocal microscopy will be used to image and quantify epidermal innervation. Since epidermal nerve fibers include nociceptors, tumor-evoked proliferation and enhanced excitability of these fibers may contribute to cancer pain. These studies will provide new information on functional interactions between tumors and peripheral nerve. Results may have a direct impact on the future development of novel medications for cancer pain that act peripherally at the tumor/nerve level.

描述：（从申请人的摘要中） 癌症引起的疼痛极大地促进了侵蚀 患者的生活质量虽然经常受到有效管理 使用麻醉品，与这些相关的许多不良副作用 药物限制了它们的使用。新有效治疗的发展 对于癌症的疼痛受到了关于基本知识的缺乏的阻碍 癌症疼痛的神经生物学机制。我们参与了 开发癌症疼痛的动物模型，该模型将允许严格 探索潜在机制和特定假设的测试。在 拟议的研究，一种使用行为的多学科方法， 电生理和形态学方法将用于研究 使用新开发的鼠模型的癌症疼痛的外围机制。我们的 初步研究表明，皮下植入后的肿瘤生长 进入后爪的溶裂性纤维肉瘤细胞导致机械 同侧爪上的痛觉过敏。我们将研究肿瘤的影响 皮肤皮肤伤害感受器的兴奋性和形态学增长 上覆盖肿瘤。在电生理记录中，我们将确定 伤害感受器是否自发活跃，并且对 天然刺激（机械，热和冷）。此外，我们将确定 肿瘤坏死因子，内皮素-1和神经生长因子的作用每个 假设在肿瘤诱发的肿瘤中分泌 伤害感受和伤害感受器的兴奋性。我们还将调查 纤维肉瘤肿瘤是否增加表皮的神经神经支配 皮肤覆盖肿瘤。免疫染色和共聚焦显微镜将用于 图像并量化表皮神经。由于表皮神经纤维包括 伤害感受器，肿瘤引起的增殖和增强的兴奋性 纤维可能会导致癌症疼痛。 这些研究将提供有关功能相互作用的新信息 肿瘤和周围神经。结果可能会直接影响未来 开发新型药物用于癌症疼痛，该药物在周围起作用 肿瘤/神经水平。