Effects of Sleep Disruption on Subjective Responses to Opioid Administration in Patients with Chronic Pain

项目总结/摘要 拟议的项目调查了实验性睡眠中断（SD）对阿片类药物反应的影响， 男性和女性慢性腰痛（CLBP）。我们认为，SD将改变两个主要因素 与阿片类药物用途：1）阿片类药物滥用倾向的测量（自我报告的“如何”指数 高”的药物让你觉得，“药物喜欢”和药物的货币估值后，急性阿片类药物 给药）和2）阿片样物质镇痛功效。我们预计，这些反应将更加明显， 慢性腰痛（CLBP）与健康对照组相比，男性的程度高于女性。我们 初步数据显示，SD对与阿片类药物滥用和阿片类药物滥用相关的几个中间因素起作用， 责任和镇痛，包括积极的影响，疼痛敏感性，以及腹侧纹状体的功能，枢纽 大脑奖励系统的一部分现有文献表明，CLBP患者可能特别容易受到 这些影响是由于异常的奖励系统神经回路。对这些性别差异的评估 关系是至关重要的，因为男性和女性在阿片类药物方面表现出不同的风险特征 成瘾、睡眠问题和疼痛。下一步是直接评估SD对阿片样物质反应的影响， 这些团体。我们提出了一个内/间设计，其中男性和女性参与者与CLBP（N=60） 和健康对照组（N=60）将经历一个晚上的SD和一个晚上的正常睡眠，在随机 秩序在每种睡眠条件下，我们将评估阿片类药物滥用倾向和镇痛效果， 氢吗啡酮，一种短效合成阿片类药物，对μ-阿片受体具有很强的亲和力，在安慰剂中， 受控累积剂量启动模式。阿片类药物滥用的责任将评估与药物的措施， 高，喜欢和多项选择程序，这将衡量药物的货币价值。 镇痛将通过涉及有害热刺激的定量感觉测试进行评估。我们假设 阿片类药物滥用倾向将增加，镇痛减少SD。我们预计这些影响 CLBP患者比健康对照组更强。在CLBP患者中，我们预计男性将 SD后阿片类药物反应的变化大于女性。这项研究填补了一个关键的知识 这一差距对解决阿片类药物流行问题具有重大影响。拟议研究的结果将为 与慢性疼痛患者使用阿片类药物相关的临床决策，并可能导致 开发针对睡眠的新型干预措施，作为减轻阿片类药物使用问题的手段。数据从 拟议的项目可能导致随后的研究，旨在确定可持续发展在多大程度上引起 阿片类药物滥用倾向和镇痛功效的改变是由推定的神经生物学介导的 机构（例如，纹状体功能），其本身可以用药理学和/或 神经刺激疗法，以防止有问题的阿片类药物使用。

PROJECT SUMMARY/ABSTRACT The proposed project investigates the effects of experimental sleep disruption (SD) on opioid response in males and females with chronic low back pain (CLBP). We propose that SD will alter two primary factors strongly related to problematic opioid use: 1) measures of opioid abuse liability (self-report indices of “how high” the drug makes you feel, “drug liking” and the monetary valuation of the drug after acute opioid administration) and 2) opioid analgesic efficacy. We expect these responses will be more pronounced in chronic low back pain (CLBP) vs. healthy controls, and in males to a greater extent than females. Our preliminary data show that SD operates on several intermediate factors associated with both opioid abuse liability and analgesia, including positive affect, pain sensitivity, and the function of the ventral striatum, the hub of the brain reward system. Extant literature suggests that CLBP patients may be especially vulnerable to these effects due to abnormal reward system neurocircuitry. The evaluation of sex differences in these relationships is essential because males and females evidence different risk profiles with respect to opioid addiction, sleep problems, and pain. The next step is to directly evaluate the effect of SD on opioid response in these groups. We propose a within/between design in which male and female participants with CLBP (N=60) and healthy controls (N=60) will experience both one night of SD and one night of normal sleep, in a random order. Following each sleep condition, we will evaluate the opioid abuse liability and analgesic efficacy of hydromorphone, a short-acting synthetic opioid with strong affinity for the μ-opioid receptor, in a placebo- controlled cumulative dose run-up paradigm. Opioid abuse liability will be assessed with measures of drug high, liking and the multiple choice procedure, which will measure the monetary valuation of the drug. Analgesia will be assessed with quantitative sensory testing involving noxious thermal stimuli. We hypothesize that opioid abuse liability will be augmented and analgesia diminished by SD. We expect those effects to be stronger in patients with CLBP than healthy controls. Among CLBP patients, we anticipate that males will evidence greater changes in opioid response following SD than females. This study fills a critical knowledge gap with major implications for addressing the opioid epidemic. Findings from the proposed study will inform clinical decision making related to the use of opioids for patients with chronic pain, and may lead to the development of novel interventions targeting sleep as a means to mitigating problematic opioid use. Data from the proposed project could lead to subsequent studies designed to determine the extent to which SD-induced alterations in opioid abuse liability and analgesic efficacy are mediated by putative neurobiological mechanisms (e.g., striatal function), which could themselves be targeted with pharmacological and/or neurostimulation therapies in an effort to prevent problematic opioid use.