Affective and Inflammatory Reactivity to Pain in Opioid Use Disorder

项目总结/摘要 我们建议调查成人阿片类药物使用者对疼痛的情感反应对结果的贡献 disorder.疼痛一直是非医疗处方阿片类镇痛药急剧增加的关键因素 滥用和阿片类药物使用障碍的流行。在阿片类药物使用障碍患者中，疼痛与 增加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， 而不是疼痛本身，是负面结果的关键因素。疼痛反应--特别是情感性的 对疼痛刺激的反应--与慢性精神分裂症患者的阿片类药物渴求和药物滥用有关 痛苦阿片类镇痛剂提供了对疼痛的情感成分的有力缓解，并且因此是高度可接受的。 在负面情绪升高的背景下，负面强化。因此，在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，过量）。此外，外设Pro 炎性细胞因子在疼痛后增加，并且与对疼痛的更大的情感反应性相关， 以及阿片类药物增强的增强性能。然而，提高情感和 阿片类药物使用障碍结果的炎症反应性疼痛仍然是未知的。值得注意的是， 反应性和外周炎性细胞因子水平可以通过干预来改变。因此， 这些因素对负面结果的贡献可以用来为那些 阿片类药物使用障碍因此，我们的目标是研究疼痛反应性和短-（阿片类） 渴望）和长期（阿片类药物复吸）的结果在成人阿片类药物使用障碍。拟定研究 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 主要使用处方阿片类药物目的1是确定情感性疼痛反应性对 对阿片类药物的渴望在这个目标中，我们将随机参与者接受一个简短的操作，减少情感 对疼痛的反应性或控制操作，随后是实验室疼痛诱导。目标2是量化 30天内对疼痛的情感和炎症反应增强与阿片类药物使用之间的相关性 开始治疗后。这项研究的结果将提供有关特定的重要信息。 行为和生理因素，将疼痛与阿片类药物使用障碍患者的结果联系起来。通过专注 在可改变的因素--负面情绪和外周炎症细胞因子水平上，这些发现可以 最终用于开发新的治疗方法，以改善阿片类药物使用者的结局 disorder.

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.