Modified Project Summary/Abstract Section This proposal responds to NOT-OD-20-101 to address the need to effectively reduce stigma related to the treatment of chronic pain in the context of the opioid crisis. Patients with chronic low back pain (CLBP) frequently have high levels of depressive and anxiety symptoms, termed “high negative affect (NA)”, and are often treated with opioid therapy. Chronic pain, mental health, and opioid use are all associated with stigma, the devaluation of a person due to the person exhibiting certain characteristics. Stigma, across these domains, is associated with decreased treatment seeking, poor treatment adherence, increased depression, greater pain, and overall worse treatment outcomes. However, these types of stigma do not operate in silos. Instead the intersectionality of health-related stigma (IHRS) may have synergistic effects. However, no studies to date examine IHRS in relation to chronic pain, opioid use, and mental health. Moreover, there is a need to develop evidence-based interventions to reduce pain and opioid related stigma that can be widely implemented. The present project will capitalize on the comparative effectiveness trial of antidepressant medication, Enhanced Fear Avoidance Rehabilitation (EFAR), or their combination in 300 patients with chronic low back pain and high negative affect. In this proposal we will examine IHRS as a potential treatment moderator and determine the preliminary efficacy of EFAR to reduce pain, opioid, and mental health stigma. Moreover, we will collect qualitative data from participants in the trial that will inform the further development of a stigma reducing intervention that can be implemented by physical and occupational therapists. This mixed-method approach will not only extend the study of intersectional stigma to the domains of chronic pain, opioid use, and mental health, but will allow us to better understand the needs of this patient population. Gathering qualitative data will help us move from Stage 0 to Stage 1 intervention development, allowing for timely intervention refinement and implementation. In sum, these findings may have implications for the development and refinement of a stigma-reducing intervention that can be widely implemented across disciplines thereby improving access and effectiveness of chronic pain and opioid use prevention, management, and treatment strategies.