HEAL Initiative: Pain Research Enhancement Program (PREP) (R15 Clinical Trial Optional)

The HEAL Initiative: Pain Research Enhancement Program (PREP), issued under funding opportunity RFA-AT-25-003, is an effort led by the National Institutes of Health (NIH) to support rigorous, interdisciplinary, small-scale pain research through R15-eligible institutions. It is funded by the National Center for Complementary and Integrative Health (NCCIH) in collaboration with several other NIH institutes including the NIA, NIAAA, NIAMS, NICHD, NIDCR, and NINDS. This opportunity is part of the broader NIH Helping to End Addiction Long-term (HEAL) Initiative®, which addresses the dual crises of opioid misuse and chronic pain by expanding research efforts across disciplines and institutions. PREP aims to achieve three major objectives: advancing basic and mechanistic pain research, fostering collaborative partnerships between R15-eligible institutions and other domestic institutions, and enhancing student involvement in pain research. Applications must propose hypothesis-driven studies relevant to pain, such as investigations of acute, chronic, neuropathic, musculoskeletal, or cancer-related pain, using preclinical models, mechanistic clinical trials, or observational methods. Only specific clinical trial types—Basic Experimental Studies with Humans (BESH) and mechanistic trials—are eligible, while efficacy or safety-focused trials are excluded. Additionally, projects must be feasible within a three-year period and include plans to actively engage students in the research process. The program prioritizes collaborative interdisciplinary partnerships with U.S.-based research institutions, which are expected to contribute unique resources or expertise. Subawards are required but may not exceed one third of the total budget. The principal investigator must be from the R15-eligible institution and lead the project. A detailed Team Management Plan is required, outlining coordination, shared leadership, intellectual property arrangements, and student engagement strategies. Likewise, a Facilities & Other Resources document must describe the impact on the institution’s research environment and student development. Applications are expected to align with NIH standards for scientific rigor, including adequate blinding, randomization, power calculations, data management, and transparent reporting. Compliance with the NIH HEAL Data Sharing Policy is mandatory, requiring submission of metadata, use of common data elements, and uploading data to a HEAL-compliant repository. HEAL awardees must also register studies, participate in annual scientific meetings, and are encouraged to engage with the PURPOSE mentorship network. The total program funding is estimated at $1.25 million per year, with up to three awards anticipated annually for FY 2026 and FY 2027. The maximum direct cost per project is $375,000 over three years. The current application cycle opens on September 29, 2025, and closes on October 28, 2025, with a letter of intent due 30 days prior. A second cycle is scheduled to open on the same date in 2026. Each submission undergoes NIH’s two-stage peer-review process with awards expected to begin in July following the application deadline. This opportunity is recurring annually with the next cycle expected to open in September 2026.