ROLE OF MELATONIN IN SECONDARY INSOMNIA IN THE ELDERLY

慢性失眠影响高达30%的老年人， 影响生活质量和日间功能。它往往是次要的， 其他医疗条件，如骨关节炎疼痛。 最近的工作已经 表明褪黑激素，一种由松果体产生的神经激素， 由视交叉上核（主要的昼夜节律起搏器）调节， 减少老年失眠症患者。然而，在初级治疗试验中， 失眠症患者的态度模棱两可。这引发了许多关于 褪黑激素的功能，如它在睡眠-觉醒调节中的作用，以及它是否 具有促进夜间睡眠的作用。有趣的是，疼痛和非类固醇 消炎药会减弱褪黑激素的节律。因此，我认为， 褪黑激素的分泌在患有慢性疼痛的老年人中受损， 会导致失眠为了解决这一假设，申请人 本研究的目的是：1）进行病例对照研究，验证假设 褪黑激素缺乏是老年人失眠的危险因素， 骨关节炎疼痛和确定一个阈值水平，以区分褪黑激素 缺陷型患者; 2）一项随机、双盲、安慰剂对照试验， 褪黑激素替代治疗老年失眠症伴骨关节炎疼痛 为了验证褪黑激素缺乏是他们的病因的假设， 失眠的发展。分析将包括单变量和多变量 Aim 1的模型和受试者操作曲线分析，以及 褪黑激素与安慰剂治疗组对目标2的客观参数的影响。这 该方案可能为神经激素风险因素提供新的见解， 发展失眠，测试模型，褪黑激素缺乏是一个因果关系 失眠因素，提供针对性褪黑激素的机制基础 替代疗法，并提供必要的培训，以进行严格的， 独立资助的以病人为导向的研究

Chronic insomnia affects up to 30% of the elderly and significantly impairs quality of life and daytime functioning. It is often secondary to other medical conditions, such as pain from osteoarthritis. Recent work has suggested that melatonin, a neurohormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, the primary circadian pacemaker, is decreased in elderly insomniacs. However, treatment trials in primary insomniacs have been equivocal. This has raised many questions regarding the function of melatonin such as its role in sleep-wake regulation and whether it has nocturnal sleep-promoting effects. Interestingly, pain and non-steroidal anti-inflammatory drugs blunt melatonin rhythms. Thus, I believe that melatonin secretion is impaired in the elderly with chronic pain and that this contributes to their insomnia. To address the hypothesis, the applicant proposes the following aims: 1) A case-control study to test the hypothesis that melatonin deficiency is a risk factor for insomnia in the elderly with osteoarthritis pain and identify a threshold level to distinguish melatonin deficient patients; 2) A randomized, double-blind, placebo controlled trial of melatonin replacement therapy in elderly insomniacs with osteoarthritis pain to test the hypothesis that melatonin deficiency is a causal factor for their development of insomnia. Analysis will include univariable and multivariable models, and receiver operator curve analysis for Aim 1, and comparison of melatonin vs. placebo treatment arms on l objective parameters for Aim 2. This protocol may provide new insights into the neurohormonal risk factors for the development of insomnia, test the model that melatonin deficiency is a causal factor for insomnia, provide a mechanistic basis for targeted melatonin replacement therapy, and provide the training necessary to conduct rigorous, independently-funded, patient-oriented research.