Chronic opioids and aging

慢性阿片类药物与衰老

• 批准号: 7234188
• 负责人: DRAKE MORGAN
• 金额: $ 21.98万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7234188
• 关键词: Absence of pain sensation; Acute; Age; Age-Years; Aging; Analgesics; Animal Model; Animals; Attenuated; Behavior; Behavioral; Blood specimen; Body Composition; Body Temperature; Censuses; Chronic; Classification; Clinical; Cognitive; Communities; Condition; Data; Dependence; Development; Disruption; Drug Kinetics; Elderly; Equilibrium; Evaluation; Fatty acid glycerol esters; Fentanyl; General Practitioners; Goals; Health; Human; Hyperalgesia; Implant; Institutes; Lead; Learning; Long-Term Effects; Longevity; Magnetic Resonance Imaging; Measures; Medical; Memory; Morphine; NIH Program Announcements; Narcotics; National Institute of Drug Abuse; Nociception; Non-Malignant; Numbers; Opioid; Outcome; Pain; Pain management; Performance; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Physiologic Thermoregulation; Physiological; Population; Pre-Clinical Model; Prevalence; Primary Care Physician; Range; Rate; Rattus; Risk; Rodent; Rodent Model; Saline; Specialist; Speed; Sucrose; Swimming; Testing; Time; Training; Treatment Protocols; United States; Week; Withdrawal; age group; age related; aged; base; behavior measurement; chronic pain; day; disability; experience; follow-up; frontal lobe; functional disability; interest; opioid abuse; osmotic minipump; prescription document; prescription procedure; research study; sensor; treatment effect

DESCRIPTION (provided by applicant): This year In the United States, "baby boomers" are beginning to turn 60 years old at the rate of nearly 8000 people per day. The proportion of the US population aged >65 years is projected to increase from 12.4% in 2000 to 19.6% in 2030; this represents an increase from 35 million to an estimated 71 million persons. Chronic pain is 1) common among community-dwelling older persons with prevalence estimates that range from 15 to 50%, 2) is associated with declining physical performance and functional dependence, and 3) when treated, attenuates declining performance and slows the progression toward disability. Given that growing numbers of older persons are seeking treatment for chronic pain from primary care physicians, and that chronic use of opioids (i.e. "narcotic" pain relievers such as morphine and fentanyl) is becoming better accepted for the treatment of many chronic pain conditions, it is inevitable that the chronic use of opioids in older persons is going to increase. Unfortunately, little is known about the long-term consequences of chronic administration of opioids, especially in older persons. The present studies are an attempt to examine the effects of chronic fentanyl administration on behavioral, pharmacological, and physiological outcomes using a well-defined rodent model of aging. Experiments in this application assess the short and long-term consequences of fentanyl administration to rats of different ages (the range is equivalent to 30 to 80 years of age in humans). The effects of this treatment will be examined on a number of physical performance measures (swim speed, agility, balance), cognitive tasks (learning and memory), and operant behavior (goal-directed responding). In addition, physiological outcomes that are directly related to the pharmacological actions of fentanyl including changes to body temperature regulation, analgesia (pain relief), and the potential development of hyperalgesia (increase in pain sensitivity) will be compared across ages. Finally, a more exploratory aim will assess fentanyl's effects on a known contributor to declining physical performance, changes in body composition (i.e. redistribution of lean versus fat mass assessed using magnetic resonance imaging). These assessments will be made over four weeks of chronic drug administration and a subsequent month-long withdrawal period. These experiments will identify potential risks and consequences of chronic opioid administration that vary as a function of age, and have implications for the increasing use of chronic opioid treatment in older persons for the management of pain. This application is directly responsive to the objectives of the current PA and the strategic aims of NIDA (as well as the National Institute on Aging) in that it establishes a preclinical model that will have direct translational implications for the evaluation of the long-term consequences of opioid administration to declining physical and cognitive performance, allowing an assessment of the potential abuse- related problems associated with this treatment regimen in the context of age-related pain. Opioids (narcotic pain relievers) are being used more for the treatment of pain although little is known about the consequences of chronic administration of these drugs, especially in older persons. Using rodents is necessary because study of the long-term effects of pharmacological treatment in humans would require several years of follow up, whereas initial testing in rats requires only months due to their compressed life spans. These experiments will identify potential health effects and long-term medical and behavioral consequences of chronic opioid administration that vary as a function of age, and have implications for the increasing use of chronic opioid treatment in older persons for the management of pain.

描述（由申请人提供）：今年在美国，“婴儿潮一代”开始以每天近8000人的速度开始年满60岁。美国年龄较高65岁的美国人口的比例预计将从2000年的12.4％增加到2030年的19.6％；这是从3500万人增加到估计的7100万人。慢性疼痛是1）在社区居住的老年人中常见的，患病率估计为15％至50％，2）与身体表现和功能依赖的下降有关，而3）治疗后，减弱性能下降并减慢对残疾的进展。鉴于越来越多的老年人正在寻求初级保健医生的慢性疼痛治疗，并且长期使用阿片类药物（即，诸如吗啡和芬太尼之类的“麻醉”止痛药，例如吗啡和芬太尼）正在更好地接受许多慢性疼痛状况，因此不可避免地会增加阿片类人的长期使用。不幸的是，对于长期给予阿片类药物的长期后果，尤其是在老年人中的长期后果知之甚少。本研究试图使用明确定义的衰老模型来检查慢性芬太尼给药对行为，药理和生理结果的影响。该应用程序中的实验评估了芬太尼给不同年龄大鼠的短期和长期后果（人类的范围相当于30至80岁）。该治疗的影响将检查对许多身体绩效指标（游泳速度，敏捷性，平衡），认知任务（学习和记忆）以及操作行为（目标定向反应）。此外，与芬太尼的药理作用直接相关的生理结果，包括对体温调节，镇痛（缓解疼痛）的变化以及跨性别的疼痛敏感性的潜在发展（疼痛敏感性的提高）。最后，一个更具探索性的目标将评估芬太尼对身体性能下降，身体成分变化的已知贡献者的影响（即使用磁共振成像评估的瘦质量与脂肪质量的重新分布）。这些评估将在长期的长期药物管理和随后的一个月戒断期内进行四个星期。这些实验将确定慢性阿片类药物给药的潜在风险和后果随着年龄的变化而变化，并对老年人在疼痛治疗中增加使用慢性阿片类药物治疗有影响。该应用直接响应当前PA的目标以及NIDA的战略目的（以及国家衰老研究所），因为它建立了一种临床前模型，该模型将直接转化对阿片类药物管理的长期后果的影响，以减少对潜在虐待与痛苦相关的痛苦，从而减少了与年龄相关的痛苦问题。阿片类药物（麻醉止痛药）被更多地用于治疗疼痛，尽管对这些药物的长期给药的后果知之甚少，尤其是在老年人中。使用啮齿动物是必要的，因为研究药理学对人类的长期影响需要进行几年的随访，而在大鼠中进行的初始测试仅需要几个月，这是由于其压缩寿命跨度。这些实验将确定慢性阿片类药物给药的潜在健康影响以及长期的医疗和行为后果，这些影响随着年龄的变化而变化，并对老年人对慢性阿片类药物治疗的使用增加具有影响。