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

睡眠中断对慢性疼痛患者阿片类药物主观反应的影响

• 批准号: 10358523
• 负责人: Patrick Finan
• 金额: $ 105.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10358523
• 关键词: Absence of pain sensation; Acute; Address; Adult; Affect; Affinity; American; Analgesics; Attenuated; Behavioral; Brain; Calibration; Chronic; Chronic low back pain; Corpus striatum structure; Data; Detection; Development; Dose; Epidemic; Euphoria; Evaluation; Female; General Population; Heroin; Human; Hydromorphone; Impairment; International; Intervention; Knowledge; Laboratories; Laboratory Study; Literature; Measurement; Measures; Mediating; Meta-Analysis; Modeling; Morphine; Neurobiology; Opiate Addiction; Opioid; Opioid Analgesics; Pain; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Physiological; Placebo Control; Population; Procedures; Recording of previous events; Research Design; Rewards; Risk; Risk Assessment; Risk Factors; Role; Running; Sensory; Sex Differences; Sleep; Sleep Disorders; Sleep disturbances; Standardization; Stimulus; Substance Use Disorder; Symptoms; System; Testing; Ventral Striatum; abuse liability; addiction; chronic pain patient; clinical decision-making; clinically relevant; design; experience; indexing; male; mu opioid receptors; neural circuit; neurobiological mechanism; novel; opioid abuse; opioid epidemic; opioid exposure; opioid use; pain model; pain patient; pain sensitivity; pharmacologic; prescription opioid; prevent; response; sex; standard measure; synthetic opioid

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.

项目摘要/摘要 拟议的项目研究了实验睡眠中断（SD）对阿片类药物反应的影响 慢性下腰痛（CLBP）的男性和女性。我们建议SD会改变两个主要因素 与有问题的阿片类药物使用密切相关：1）阿片类药物滥用责任的度量（自我报告指数 高高的”药物让您感到“毒品喜欢”和急性OOid后药物的货币价值 给药）和2）绿核酸镇痛效率。我们希望这些回应会更明显 慢性下腰痛（CLBP）与健康对照，在男性中比女性更大。我们的 初步数据显示，SD在与阿片类药物滥用相关的几个中间因素上运行 责任和镇痛，包括积极影响，疼痛敏感性以及腹侧纹状体的功能，轮毂 大脑奖励系统的。现存的文献表明，CLBP患者可能特别容易受到影响 这些影响由于异常奖励系统神经记录。这些性别差异的评估 关系是必不可少的，因为男性和女性证明了与Ooid有关的不同风险特征 成瘾，睡眠问题和痛苦。下一步是直接评估SD对阿片类药物反应的影响 这些群体。我们提出了A内部/在设计之间/女性参与者（n = 60）的设计中 健康的对照（n = 60）将随机遇到一个晚上的SD和一个正常睡眠的晚上 命令。遵循每个睡眠状况，我们将评估阿片类药物滥用责任和镇痛效率 在安慰剂中，水电性是一种对μ阿片受体的较强作用的合成阿片类药物， 受控的累积剂量成量范式。阿片类药物滥用责任将通过药物测量评估 高，喜欢和多项选择程序将衡量药物的货币价值。 镇痛将通过定量感觉测试评估涉及有害热刺激。我们假设 SD将增加阿片类药物滥用责任，镇痛减少。我们希望这些影响会 CLBP患者比健康对照组强。在CLBP患者中，我们预计男性会 证据与女性相比，SD后阿片类药物反应的变化更大。这项研究填补了批判知识 差距具有解决阿片类药物流行病的主要影响。拟议研究的发现将告知 与使用阿片类药物用于慢性疼痛患者有关的临床决策，并可能导致 开发针对睡眠的新型干预措施，作为减轻有问题的阿片类药物使用的一种手段。来自 拟议的项目可能导致随后的研究旨在确定SD诱导的程度 推定的神经生物学介导了卵巢滥用责任和镇痛效率的改变 机制（例如，纹状体功能）本身可以用药物和/或针对 神经刺激疗法以防止有问题的阿片类药物使用。