Cognitive, Behavioral and Aging Effects of Opioids in Alcohol Users

 描述(由申请人提供)：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费用估计超过5000亿美元。疼痛在老年人中的患病率最高，通常与严重的身体和心理社会残疾有关。社区老年人中持续性疼痛问题的流行率估计在30%到80%之间。越来越多的证据表明，慢性疼痛与酒精使用障碍之间存在联系，这在老年人中非常令人担忧。长期不健康的酒精使用可能会改变疼痛的主观体验和对止痛药的反应，这可能会使疼痛的有效临床治疗复杂化或妥协。特别是，老年人使用不健康的酒精可能会加剧阿片类药物使用造成的虚弱副作用，如认知受损、协调性和平衡性减弱，以及摔倒的风险增加，从而威胁到独立生活。此外，不健康的酒精使用可能会增加止痛药的滥用可能性。然而，在老年人中，不健康的酒精使用对阿片类镇痛剂的药代动力学和药效学的影响还没有研究。我们的总体目标是在一项受控的人体实验室研究中调查衰老和酒精使用对阿片类镇痛剂反应的影响。我们将比较急性口服测试剂量羟考酮后疼痛缓解以及主观、认知和强化副作用，这些患者包括以下轻度到中度复发性疼痛的受试者：1)不健康饮酒水平的老年人(&gt；65岁)；2)健康饮酒水平的老年人；3)不健康饮酒水平的中年人(35-55岁)；4)健康饮酒水平的中年成年人。“PA-13-058老龄化中的疼痛”呼吁进行研究，研究影响老年人疼痛体验和治疗的因素的机制和过程，包括酒精使用和疼痛的相互作用。建议的受管制人士 实验室研究是创新的，因为它可能在人类身上提供第一个高度 在阿片类止痛剂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药物反应之间的相互作用是合理的，但迄今未经证实。如果被证实是真的，这可能会导致深入研究过度饮酒对疼痛患者长期阿片类药物治疗的有效性、耐受性和安全性的混杂影响。

 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.