Affective and Inflammatory Reactivity to Pain in Opioid Use Disorder

项目摘要/摘要 我们建议调查成人使用阿片类药物后，情感反应对疼痛的影响。 无序。疼痛一直是非医疗处方阿片类止痛药急剧上升的关键因素 滥用和阿片类药物使用障碍的流行。在有阿片类药物使用障碍的人中，疼痛与 增加对阿片类药物的渴望和复发的风险。对患有慢性疼痛的成年人的研究发现，疼痛的反应性， 而不是痛苦本身，是造成负面结果的关键因素。疼痛反应--尤其是情感反应 对疼痛刺激的反应--与阿片类药物渴求和药物滥用有关 疼痛。阿片类镇痛剂能有效缓解疼痛的情感成分，因此对 在负面情绪高涨的背景下，负面强化。因此，在那些使用阿片类药物的人中 精神障碍，对疼痛的情感反应增强可能会增加使用阿片类药物缓解的动机，尽管 负面后果(例如，失业、失去家庭支持、吸毒过量)。此外，外设PRO- 炎性细胞因子在疼痛后增加，并与对疼痛的更大情感反应有关，如 以及增强阿片类药物的增强性能。然而，情感和情感的增强的影响 阿片类药物使用障碍对疼痛的炎症反应结果尚不清楚。值得注意的是，两者都很有感情 可通过干预改变反应性和外周血炎性细胞因子水平。因此，理解 这些因素对负面结果的贡献可以被用来指导那些 有阿片类药物使用障碍。因此，我们的目标是调查疼痛反应性和短期(阿片类药物) 阿片类药物使用障碍成年人的长期(阿片类药物复发)结果。建议进行的研究 包括两个目标，我们建议招募患有阿片类药物使用障碍和慢性疼痛的男性和女性 他们主要使用处方阿片类药物。目标1是确定情感疼痛反应性对 对阿片类药物的渴望。在这一目标中，我们将随机让参与者接受一种减少情感因素的简短操作 对疼痛的反应性或控制手法，然后进行实验室疼痛诱导。目标2是量化 30天内对疼痛和阿片类药物使用的情感和炎症反应增强之间的关系 在开始治疗后。这项研究的结果将提供关于特定的 将疼痛与阿片类药物使用障碍患者的结果联系起来的行为和生理因素。通过聚焦 关于可改变的因素--负面情绪和外周炎症细胞因子水平--这些发现可以 最终被用来为新疗法的开发提供信息，以改善阿片类药物使用者的结果 无序。

Project Summary/Abstract We propose to investigate the contribution of affective reactivity to pain to outcomes in adults with opioid use disorder. Pain has been a critical factor in the dramatic escalation of nonmedical prescription opioid analgesic misuse and the epidemic of opioid use disorder. Among those with opioid use disorder, pain is associated with increased opioid craving and risk for relapse. Studies in adults with chronic pain have found that pain reactivity, rather than pain itself, is a key contributor to negative outcomes. Pain reactivity--particularly affective responding to painful stimuli--is associated with opioid craving and medication misuse in adults with chronic pain. Opioid analgesics provide powerful relief of the affective component of pain, and thus are highly negatively reinforcing in the context of elevated negative affect. Accordingly, among those with opioid use disorder, heightened affective reactivity to pain may increase motivation to use opioids for relief, despite negative consequences (e.g., unemployment, loss of family supports, overdose). Furthermore, peripheral pro- inflammatory cytokines increase following pain, and are associated with greater affective reactivity to pain as well as enhanced reinforcing properties of opioids. However, the impact of heightened affective and inflammatory reactivity to pain on opioid use disorder outcomes remains unknown. Notably, both affective reactivity and peripheral inflammatory cytokine levels can be modified with intervention. Thus, understanding of the contribution of these factors to negative outcomes can be used to inform treatment development for those with opioid use disorder. Therefore, our objective is to investigate pain reactivity and both short- (opioid craving) and long-term (opioid relapse) outcomes in adults with opioid use disorder. The proposed study consists of two aims for which we propose to recruit men and women with opioid use disorder and chronic pain who predominantly use prescription opioids. Aim 1 is to determine the contribution of affective pain reactivity to opioid craving. In this aim, we will randomize participants to receive a brief manipulation that reduces affective reactivity to pain or a control manipulation, followed by a laboratory pain induction. Aim 2 is to quantify the association between heightened affective and inflammatory reactivity to pain and opioid use in the 30 days after initiating treatment. The results from this study will provide important information about the specific behavioral and physiological factors that link pain to outcomes in those with opioid use disorder. By focusing on modifiable factors—negative affect and peripheral inflammatory cytokine levels—these findings can ultimately be used to inform the development of novel treatments to improve outcomes in those with opioid use disorder.