Biobehavioral basis of knee OA

显示与AD/ADRD相关的拟议研究摘要 对疼痛的敏感性取决于上行和下行疼痛的活动平衡。 小路。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。 正在处理。在人类中研究这一系统的成熟工具是条件性疼痛调制 (CPM)范式，其中测试刺激的疼痛强度等级是在存在和 缺乏伴随的远程应用的条件性刺激。更多消极的CPM响应(= 同时刺激下疼痛强度降低)表明内源性止痛 (即，增加疼痛抑制)，并由脊椎-球-脊髓反射介导，该反射由 大脑皮质较高的区域。考虑到下行疼痛调制所需的相同脑区 对阿尔茨海默病(AD)、异常下行疼痛的患者也有负面影响 抑制可能参与了AD患者疼痛处理的改变。据我们所知，到目前为止还没有研究 探讨阿尔茨海默病患者下行疼痛抑制及其机制。这个 拟议的补充方案将招募50名被诊断为患有和不伴有疼痛的轻度AD的老年人，并 进行条件性疼痛调制、认知功能电池和多项功能的实验 模式神经成像与家长R01奖中使用的方法一致，并与 认知完好的膝骨性关节炎患者。拟议的研究针对的是 在文献中的显著差距，并将是第一个评估与疼痛相关的神经变化的人 阿尔茨海默病患者和非阿尔茨海默病患者与疼痛相关的底物。密钥的自上而下的识别 受疼痛和阿尔茨海默病影响的调制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人面临患上阿尔茨海默病的风险。

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.