Mechanisms of Cancer Therapy Induced Pain

疼痛的神经病变是长春新碱、紫杉醇和顺铂化疗的主要剂量限制因素，经常迫使患者退出本来可以治愈的治疗。此外，化疗引起的疼痛难以治疗，往往会持续存在于癌症幸存者身上，造成长期的残疾和痛苦。因为这些药物是治疗大量淋巴和实体肿瘤的首选药物，数十万 每年都有患者受到这种神经病变的影响。该项目的长期目标是确定化疗引起的疼痛的机制，并确定缓解和预防疼痛的潜在治疗干预措施。在这里，我们建议在互补研究中的两个特定目标中测试与这一目标相关的两个假设，这些人是 正在接受紫杉醇或顺铂化疗的。 假设1：化疗由于优先损害有髓初级传入纤维功能而导致神经病理性疼痛。具体目标1：在接受非小细胞肺癌和乳腺癌化疗的患者中，将每隔三周使用定量感觉测试来确定初级传入功能。出现疼痛的患者的结果将与正常志愿者的结果以及来自 不要产生疼痛。 假设2：化疗引起的疼痛与血清细胞因子水平升高有关。 具体目标2：在接受肺癌和乳腺癌化疗的患者中，将以与上述相同的时间间隔检测血清细胞因子水平。出现疼痛的患者的结果将与不出现疼痛的患者的结果形成对比。 总而言之，这个项目将深入了解化疗引起的疼痛的机制，主要剂量限制 一线化疗药物的副作用。该项目的成功将导致确定近期治疗候选方案，以便在一个更大、更深入的提案中进行评估，该提案可能会影响癌症幸存者的生存、生活质量和恢复生产力。

Painful neuropathy is the principal dose-limiting factor in chemotherapy with vincristine, taxol and cisplatin and often forces patients to withdrawal from what could otherwise be curative therapy. Moreover, chemotherapy-induced pain is refractory to treatment and often persists in cancer survivors producing prolonged disability and suffering. In that these drugs are the treatment of choice for a multitude of lymphoid and solid tumors, hundreds of thousands of patients each year are affected by this neuropathy. The long-term goal of this project is to determine the mechanism of chemotherapy-induced pain and identify potential therapeutic interventions for its relief and prevention. Here we propose to test two hypotheses related to this goal in two specific aims in complementary studies in humans who are undergoing chemotherapy with taxol or cisplatin. Hypothesis 1: Chemotherapy induces neuropathic pain due to a preferential impairment of myelinated primary afferent fiber function. Specific Aim 1: Quantitative sensory testing will be used to define primary afferent function at three week intervals in patients as they undergo chemotherapy for non-small cell lung cancer and breast cancer. The results in patients who develop pain will be contrasted with those in normal volunteers and with data from patients who do not develop pain. Hypothesis 2: The onset of chemotherapy induced pain is associated with increases in serum cytokine levels. Specific Aim 2: Blood serum levels of cytokines will be measured at the same intervals as above in patients as they undergo chemotherapy for lung and breast cancer. The results in patients who develop pain will be contrasted with that in patients who do not develop pain. In summary this project will yield insight to the mechanisms of chemotherapy-induced pain, the major dose limiting side effect of front-line chemotherapeutic drugs. Success in this project will result in the identification of near-term treatment candidates for evaluation in a larger more in-depth proposal that has the potential to impact on the survival, quality of life and return to productivity of cancer survivors.