Pain Sensitivity and Unpleasantness in People with Alzheimer's Disease and Cancer

项目总结 此多站点(范德比尔特大学医学中心[VUMC]和俄亥俄州立大学[OSU])R01应用程序 是对PA-18-502--推进老年姑息治疗科学的回应而提交的。这项建议 检查4期乳腺癌和前列腺癌对疼痛敏感性和疼痛的心理物理测量的影响 阿尔茨海默病(AD)中的不愉快。相当数量的老年人会患上癌症和 共同发生的阿尔茨海默病将他们置于治疗癌症疼痛的极大风险中。了解以下方面的影响 癌症和AD对疼痛感知的影响将为AD中的癌症疼痛提供关键的见解。不幸的是， 未经治疗的癌症疼痛的后果可能是毁灭性的。超过50%的住院癌症患者 将他们的痛苦描述为“令人痛苦、可怕或折磨人”。目前尚不清楚癌症和阿尔茨海默氏症是如何 疾病改变了疼痛的处理。疼痛处理过程的改变可能会进一步增加疼痛检测能力下降的风险 一旦受伤，就会增加未得到治疗的转移性癌症疼痛的风险，并可能倾向于增加 痛苦。如果我们的结果确定癌症和共生的阿尔茨海默病使这些人处于 增加痛苦的风险、有针对性的止痛药开发战略和/或量身定做的干预措施，以 然后，可以为这一高度脆弱和研究不足的人群设计最大限度的疼痛治疗。 我们将研究热痛和压痛阈值以及中枢敏化(通过时间评估 总计)在每个部位按分组平衡的132人的疼痛(总计为264人)：132名男性(44人，4期) 前列腺癌，44例患有AD和4期前列腺癌，44例仅患有AD)和132名女性(44例分期 4例乳腺癌，44例AD和4期乳腺癌，44例单纯AD)。我们的总体假设是 与仅患有AD的老年人相比，患有4期乳腺癌和前列腺癌疼痛的老年人会发生疼痛 中枢神经系统敏感化，有每天经历剧烈癌症疼痛的风险，以及患有AD的人，大脑 损伤导致中枢神经系统疼痛处理的进一步改变，从而降低识别和 准确地自我报告疼痛，增加癌症疼痛得不到治疗的风险，并可能倾向于增加 在生命的尽头遭受痛苦。 我们设计了拟议的研究，以最大限度地减少参与研究的负担，使受试者 和他们的照顾者尽可能舒适，包括收集所有研究数据，无论参与者 居所，如家庭、辅助生活或疗养院。总而言之，很少有研究 研究癌症和共生的阿尔茨海默病对疼痛感知的影响，没有 在这一人群中关于疼痛的对照实验研究。这项拟议的研究是第一次测试痛觉阈值。 以及在这个研究不足的人群中的认知。结果可能立即帮助指导这种高度疼痛的护理 老年人中的弱势群体。

PROJECT SUMMARY This multi-site (Vanderbilt University Medical Center [VUMC] and Ohio State University [OSU]) R01 application is submitted in response to PA-18-502--Advancing the Science of Geriatric Palliative Care. This proposal examines the impact of stage 4 breast and prostate cancer on psychophysical measures of pain sensitivity and unpleasantness in Alzheimer's disease (AD). A considerable number of older adults will suffer from cancer and co-occurring AD placing them at great risk of suffering under treated cancer pain. Understanding the impact of cancer and AD on pain perception will provide key insights into cancer pain in AD. Unfortunately, the consequences of untreated cancer pain can be devastating. More than 50% of hospitalized patients with cancer described their pain as `distressing, horrible, or excruciating'. It remains unknown how cancer and Alzheimer's disease alter pain processing. Altered pain processing may further increase the risk for reduced detection of pain upon injury, increase the risk for under treatment of metastatic cancer pain, and may predispose to increased suffering. If our results determine that cancer and co- occurring Alzheimer's disease place these individuals at risk of increased suffering, targeted analgesic drug development strategies, and/or tailored interventions to maximize pain treatment can then be designed for this highly vulnerable and under studied population. We will study thermal and pressure pain thresholds as well as central sensitization (assessed via temporal summation) to pain in 132 people balanced by group at each site (total n=264):132 males (44 with stage 4 prostate cancer, 44 with AD and stage 4 prostate cancer, and 44 with AD only) and 132 females (44 with stage 4 breast cancer, 44 with AD and stage 4 breast cancer, and 44 with AD only). Our overall hypothesis is that when compared to older adults with AD only, older adults with stage 4 breast and prostate cancer pain develop CNS sensitization and are at risk of experiencing intense daily cancer pain, and in those with comorbid AD, brain damage leads to further alterations in CNS pain processing which decreases the ability to recognize and accurately self-report pain, increases the risk of under treatment of cancer pain, and may predispose to increased suffering at the end of life. We have designed the proposed study to minimize the burden of participating in research to make the subjects and their caregivers as comfortable as possible including collecting all study data wherever the participant resides such as home, assisted living, or nursing homes. To summarize, there are extremely few studies examining the impact of cancer and co-occurring Alzheimer's disease on pain perception and there are no controlled experimental studies of pain in this population. The proposed study is the first to test pain threshold and perception in this under-studied population. Results may immediately help guide pain care in this highly vulnerable group of older adults.