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.