The Effect of Chronic Pain on Delay Discounting in Methadone Patients

项目摘要/摘要 这份R21重新提交的报告建议系统地研究慢性 美沙酮患者的肌肉骨骼疼痛、延迟折扣、阿片类药物戒断和疼痛灾变 阿片类药物使用障碍的维持(OUD)。阿片类药物过量死亡的流行继续上升，导致 2017年的人数比艾滋病毒/艾滋病流行最严重的时候要多。药物辅助治疗，利用 美沙酮或丁丙诺啡，是治疗OUD的标准护理。然而，同时发生的慢性 疼痛会降低治疗效果，并与复发和治疗中的保留力差有关。机制 慢性疼痛可能通过哪些因素影响抑郁症患者的冲动决策(例如，药物复发) 还没有被很好地定性。影响药物使用决定的两个因素是冲动和急躁 阿片类药物戒断。延迟贴现是一种冲动性决策模型，指的是观察到 推迟结果会降低其主观价值。尽管延迟折扣最初被认为是 最近有研究表明，与特征类似的情景应激源可以增加折扣，包括急性阿片类药物 戒烟。目前还不知道慢性应激源(即慢性疼痛)是否对折扣有类似的影响，或者是否 在急性和慢性应激源同时存在的情况下，折扣的变化比任何一种都要大 单独的压力源。特质疼痛灾难被认为增加了对疼痛的关注和关注，并影响了 选择用来应对疼痛的应对策略。它可以在冲动的决定中发挥重要作用 以禁欲为代价使用药物来立即缓解疼痛，特别是作为慢性疼痛的一种功能。这 提案将测试慢性疼痛如何与OUD中冲动决策的增加相关，无论是 使用和不使用阿片类药物的OUD患者在接受阿片类药物戒断时的冲动决策更大 慢性疼痛，以及灾难如何改变慢性疼痛和冲动决定之间的联系- 制作。这项拟议的研究将招募两组接受美沙酮治疗的患者。 有(疼痛)和无(无疼痛)慢性肌肉骨骼疼痛，与可影响的特征匹配 延迟折扣。每组将按平衡顺序进行两次双盲实验：1) 美沙酮作用高峰期间的控制条件[肌肉注射生理盐水]和2)肌肉注射 纳洛酮催促阿片类药物戒断。相同的延迟折扣任务将在 会议。具体目的是：(1)确定厌恶应激源对延迟折扣的影响 在美沙酮维持中；以及(2)调查特质疼痛灾难性改变的程度 阿片类药物戒断与延迟折扣之间的关系。如果撤军和制造灾难被发现 影响冲动决策，未来的研究可能会扩大对这些变量的研究，以确定它们是否 在决定使用阿片类药物或复发方面发挥明确的因果作用，并制定补救措施 冲动导致复发，从而改善治疗结果。

PROJECT SUMMARY / ABSTRACT This R21 resubmission proposes to systematically study the association between chronic musculoskeletal pain, delay discounting, opioid withdrawal and pain catastrophizing in patients on methadone maintenance for opioid use disorder (OUD). The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 then at the height of the HIV/AIDS epidemic. Medication assisted treatment, utilizing methadone or buprenorphine, is the standard of care for the treatment of OUD. However, co-occurring chronic pain can reduce treatment efficacy and is associated with relapse and poor retention in treatment. Mechanisms by which chronic pain may influence the impulsive decision-making (e.g., drug relapse) in persons with OUD have not been well characterized. Two factors that can influence decisions to use drugs are impulsivity and acute opioid withdrawal. Delay discounting is a model of impulsive decision-making and refers to the observation that delaying a consequence reduces its subjective value. Though delay discounting was originally thought to be trait-like, situational stressors have recently been shown to increase discounting, including acute opioid withdrawal. It is not known if a chronic stressor (i.e., chronic pain) has a similar effect on discounting or whether there are greater changes to discounting in the presence of both an acute and chronic stressor than either stressor alone. Trait pain catastrophizing is thought to increase attention and focus on pain and influence the choice of coping strategies used to respond to pain. It could play an important role in the impulsive decision to use drugs for immediate pain relief at the expense of abstinence, especially as a function of chronic pain. This proposal will test how chronic pain is associated with increases in impulsive decision-making in OUD, whether impulsive decision-making is greater when undergoing opioid withdrawal for OUD patients with and without chronic pain, and how catastrophizing may modify the association between chronic pain and impulsive decision- making. The proposed study will recruit two groups of patients maintained on methadone for OUD – individuals with (PAIN) and without (NO PAIN) chronic musculoskeletal pain, matched on characteristics that can influence delay discounting. Each group will have two double-blind experimental sessions in counterbalanced order: 1) control condition [intramuscular (IM) injection of normal saline] during peak methadone effects and 2) IM naloxone-precipitated opioid withdrawal. The same delay discounting tasks will be measured during each session. The specific aims are to: (1) Determine the effect of aversive stressors on delay discounting in persons in methadone maintenance; and (2) Investigate the degree to which trait pain catastrophizing modifies the association between opioid withdrawal and delay discounting. If withdrawal and catastrophizing were found to affect impulsive decision-making, future research could extend the study of these variables to determine if they play an explicitly causal role in decisions to use opioids or to relapse, and to develop interventions to remediate impulsivity leading to relapse, thereby improving treatment outcomes.