The National Institute of Neurological Disorders and Stroke (NINDS) and other National Institutes of Health (NIH) components intend to publish a Notice of Funding Opportunity (NOFO) to solicit applications for large-scale, multisite clinical trials that will inform clinicians about the efficacy or effectiveness of interventions or management strategies that reduce opioid use, improve functional outcomes, and reduce pain across the continuum of acute to chronic pain associated with many types of diseases, conditions, or pain presenting as a disease itself. The goal of this NOFO will be to expand the suite of evidence-based effective therapeutics to alleviate pain for multiple pain conditions to benefit patients and their families. Key aspects of this opportunity include: • The development of large-scale, multisite clinical trials to test the efficacy or effectiveness of interventions or management strategies for pain management • The focus on reducing opioid use, improving functional outcomes, and reducing pain across the continuum of acute to chronic pain • The opportunity for collaborative investigations combining expertise in testing existing pharmaceutical, repurposed therapeutics, and/or existing devices • The use of the UG3/UH3 activity code for this NOFO