Biobehavioral basis of knee OA

显示与AD/ADRD相关性的拟议研究摘要 对疼痛的敏感性取决于上升疼痛和下降疼痛的活动平衡 途径。下行疼痛控制系统通过抑制或促进伤害性感受来调节疼痛 处理.在人类中研究这一系统的成熟工具是条件性疼痛调制 (CPM)范例，其中测试刺激的疼痛强度等级是在存在和 没有伴随的、远程施加的条件刺激。更多的负面CPM响应（= 同时刺激下疼痛强度等级降低）指示内源性镇痛 (i.e.,增加的疼痛抑制），并由脊髓-延髓-脊髓反射介导， 高级大脑皮层区域。考虑到下行疼痛调制所需的大脑区域 也对阿尔茨海默病（AD）患者产生负面影响， 抑制可能有助于改变AD中的疼痛处理。据我们所知，迄今为止没有任何研究 研究了AD患者的下行疼痛抑制及其潜在机制。的 拟议的补充将招募50名被诊断患有轻度AD的老年人， 接受条件性疼痛调制的实验课程，认知功能电池和多- 模态神经成像与R 01研究中使用的方法一致，并与 患有膝关节骨关节炎但认知功能完好的个体。拟议的研究涉及一个 这是文献中的一个重大空白，将是第一个评估神经系统疼痛相关变化的人。 基质在老年人与非AD的疼痛。自顶向下的关键识别 受疼痛和AD影响的调节脑网络将增加我们对神经生物学的理解。 疼痛处理的变化可能会使个体处于发展AD的风险中。

Abstract of the proposed research that shows the relevance to AD/ADRD The susceptibility to pain depends on the balance of activity in ascending and descending pain pathways. The descending pain control system modulates pain by inhibiting or facilitating nociceptive processing. Well-established tools to study this system in humans are conditioned pain modulation (CPM) paradigms in which pain intensity ratings of test stimuli are obtained in the presence and absence of a concomitantly, remotely applied conditioning stimulus. More negative CPM responses (= reduced pain intensity ratings under concurrent stimulation) are indicative of endogenous analgesia (i.e., increased pain inhibition) and are mediated by spino-bulbo-spinal reflexes which are controlled by higher cortical brain areas. Given that the same brain regions needed for descending pain modulation are also negatively impacted in persons with Alzheimer's Disease (AD), aberrant descending pain inhibition might contribute to altered pain processing in AD. To our knowledge no studies to date have investigated descending pain inhibition in persons with AD nor its underlying mechanisms. The proposed supplement will recruit 50 older adults diagnosed with mild AD with and without pain and undergo experimental sessions of conditioned pain modulation, a cognitive function battery and multi- modal neuroimaging consistent with the methodology used in the parent R01 award and compared with individuals with knee osteoarthritis that are cognitively intact. The proposed research addresses a significant gap in the literature and would be the first to evaluate the pain-related changes in the neural substrates in older persons with and without AD in relation to pain. The identification of key top-down modulatory brain networks impacted by pain and AD will increase our understanding of neurobiological changes in pain processing that may put individuals at risk of developing AD.