Cognitive, Behavioral and Aging Effects of Opioids in Alcohol Users

 医学研究所（IOM）的一份报告表明，数百万美国人患有慢性疼痛，每年与慢性疼痛相关的医疗保健费用估计超过5000亿美元。疼痛的患病率在老年人中最高，通常与严重的身体和心理残疾有关。据估计，社区居住的老年人中持续性疼痛问题的患病率为30- 80%。越来越多的证据表明，慢性疼痛和酒精使用障碍之间的联系在老年人中引起了极大的关注。长期不健康的酒精使用有可能改变疼痛的主观体验和对止痛药的反应，这可能使疼痛的有效临床管理复杂化或妥协。特别是，老年人不健康的酒精使用可能会加剧阿片类药物使用的副作用，如认知受损，协调和平衡能力下降，以及可能威胁独立生活的福尔斯风险增加。此外，不健康的酒精使用可能会增加止痛药的滥用潜力。然而，尚未在老年人群中研究不健康饮酒对阿片类镇痛药的药代动力学和药效学的影响。我们的总体目标是在对照人体实验室研究中调查衰老和酒精使用对阿片类镇痛药反应的影响。我们将在以下轻度至中度复发性疼痛受试者中比较急性口服试验剂量羟考酮后疼痛缓解以及主观、认知和强化副作用：1）老年人（> 65岁）饮酒水平不健康; 2）饮酒水平健康的老年人; 3）中年人（35-55岁）酒精使用水平不健康; 4）酒精使用水平健康的中年人。“PA-13-058衰老中的疼痛”要求研究检查影响老年人疼痛体验和治疗的因素的机制和过程，包括饮酒和疼痛的相互作用。拟议的受控 实验室研究是创新的，因为它可能首次在人类中证明了一种高度的 在阿片类镇痛药的治疗使用和滥用倾向的临床背景下，慢性酒精使用和阿片类反应之间的相互作用似乎合理，但迄今尚未得到证实。如果被证明是真的，它可能会导致对过度饮酒对疼痛患者长期阿片类药物治疗的疗效，耐受性和安全性的混淆影响的深入研究。

 DESCRIPTION (provided by applicant): An Institute of Medicine (IOM) report indicates that millions of Americans suffer from chronic pain conditions and that annual health care costs related to chronic pain are estimated at over half a trillion dollars. The prevalence of pain is greatest amongst older adults and is often associated with significant physical and psychosocial disability. Estimates of the prevalence of persistent pain problems among community-dwelling elderly persons range from 30-80%. Increasing evidence suggests an association between chronic pain and alcohol use disorder that is of great concern in older adults. Chronic unhealthy alcohol use has the potential of altering the subjective experience of pain and response to pain medications, which could complicate or compromise the effective clinical management of pain. In particular, unhealthy alcohol use in older adults may exacerbate debilitating side effects from opioid use, such as impaired cognition, diminished coordination and balance, and enhanced risk for falls that can threaten independent living. In addition, unhealthy alcohol use could increase the abuse potential of pain medications. However, the influence of unhealthy alcohol use on the pharmacokinetics and pharmacodynamics of opioid analgesics has not been studied in the elderly population. Our overall goal is to investigate the impact of aging and alcohol use on response to opioid analgesics in a controlled human laboratory study. We will compare pain relief as well as subjective, cognitive, and reinforcing side effects after an acute oral test doseof oxycodone in the following groups of subjects with mild to moderate recurring pain: 1) older adults (> 65 yrs) with unhealthy levels of alcohol use; 2) older adults with healthy levels of alcohol use; 3) middle-aged adults (35-55 yrs) with unhealthy levels of alcohol use; 4) middle-aged adults with healthy levels of alcohol use. "PA-13-058 Pain in Aging" calls for studies that examine the mechanisms and processes by which factors impact the experience and treatment of pain in older adults, including the interaction of alcohol use and pain. The proposed controlled laboratory study is innovative in that it may provide the first demonstration in humans of a highly plausible, but heretofore unproven interaction between chronic alcohol use and opioid response in the clinical context of therapeutic use and abuse liability of opioid analgesics. If proven true it would likely lead to in-depth studies on the confounding effects of excessive alcohol consumption on the efficacy, tolerability and safety of long-term opioid therapy in pain patients.