PROJECT SUMMARY/ABSTRACT Our goal is to build Sickle Cell Disease Pain Analgesia and Integrative Network (SCDPAIN) as an innovative, dynamic and interactive platform that will advance the NCCIH's bold mission for research on pain mechanisms in sickle cell disease (SCD). Pain is one of the major comorbidities of SCD leading to poor quality of life, frequent opioid use and reduced survival. Compared to most other painful conditions, pain in SCD is unique because of the unpredictable and recurrent episodes of acute pain due to vaso-occlusive crises, in addition to chronic pain which continuously affects the majority of individuals. Pain in SCD can start during infancy and continue throughout life. Guided by an unmet need to address the morbidity associated with pain in SCD, our network is committed to profoundly impacting the science of sickle cell pain through leading expertise in pain, SCD pathobiology, end-organ damage and integrative interventions, assisted by cutting-edge technological advancement through 3 specific aims: [#1] “Science without borders.” To develop a collaborative network of multidisciplinary scientists, clinicians, analysts, and community partners to advance the understanding of SCD pain mechanisms; [#2] “Promoting the future” for innovative, technically advanced, multidimensional, multidisciplinary and holistic team science approaches; and [#3] “Hub to health,” multimodal dissemination efforts to maximize access to SCDPAIN. To achieve these goals, we will establish 6 focused working groups on, priority areas, pilot funding, sabbatical review, network foresight and review, annual review, and promotion of diversity and equity. We propose 3 critical priority areas, [i] to determine the central mechanisms involved in the persistence of pain and opioid use in SCD, [ii] study “interoception of sickle pain perception” and/or improve SCD pain responses in the brain and other organs within animals and humans, and [iii] examine chronic and acute pain and downstream complications and treatment side-effects requiring whole-person approaches. Finally, we will maximize access to SCDPAIN via multimodal dissemination efforts to propel scientific advancements in SCD. The MPI team has extensive experience in propelling SCD pain research forward, bringing multidisciplinary teams together, and mentoring the next generation of pain scientists. In addition, a team of 9 collaborators bring extensive, diverse and cutting-edge technology which will lead research into a new era of mechanism-based translational understanding of sickle cell pain. Their passion for successful mentoring and promoting diversity is poised to provide a continuum of success to the network. The impact of SCDPAIN will be monumental in: [1] Building multidisciplinary research capacity to fulfill critical unmet needs of SCD pain; [2] Incentivizing novel initiatives through Pilot funds leading to R-series, HEAL and related Grants and [3] Catalyzing the future generation of scientis...