ROLE OF MELATONIN IN SECONDARY INSOMNIA IN THE ELDERLY

慢性失眠影响高达30%的老年人，而且显著 损害生活质量和日间功能。它通常是次要的 其他医疗条件，如骨关节炎引起的疼痛。最近的工作有 提示褪黑激素，一种松果体产生的神经激素和 受视交叉上核调节，视交叉上核是主要的昼夜节律起搏器 在老年失眠症患者中有所下降。然而，初级治疗试验 失眠症患者一直模棱两可。这引发了许多关于 褪黑素的功能，如它在睡眠-觉醒调节中的作用以及它是否 对夜间睡眠有促进作用。有趣的是，疼痛和非类固醇 消炎药可以抑制褪黑激素的节律。因此，我认为 患有慢性疼痛的老年人褪黑激素分泌受损，这 导致他们失眠。为了解决这个假设，申请者 提出了以下目标：1)病例对照研究以检验假说 褪黑素缺乏是老年人失眠的危险因素 骨关节炎疼痛并确定区分褪黑激素的阈值水平 2)一项随机、双盲、安慰剂对照试验 褪黑素替代疗法治疗老年失眠症伴骨关节炎疼痛 来检验褪黑素缺乏是导致他们 失眠的发展。分析将包括单变量和多变量 模型，以及目标1的接收器操作员曲线分析，以及 褪黑素与安慰剂治疗武器对L的客观参数的目的2。 方案可能提供对神经激素风险因素的新见解 失眠的发展，检验褪黑素缺乏是一个原因的模型 失眠因素，为靶向褪黑素提供机制基础 替代疗法，并提供必要的培训，进行严格的， 独立资助、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.