The HEAL Initiative: Pain Research Enhancement Program (PREP) (R15 Clinical Trial Optional) funding opportunity, issued by the National Institutes of Health (NIH), seeks to support basic and mechanistic pain research at institutions eligible for R15 Academic Research Enhancement Awards. This program aims to improve pain research capabilities, foster interdisciplinary research partnerships, and enhance the research environment for health professional, undergraduate, and graduate students at R15-eligible institutions. The initiative is a critical component of the NIH Helping to End Addiction Long-term (HEAL) Initiative, which addresses pain management and the opioid crisis.

The program has three primary objectives: conducting small-scale basic and mechanistic pain research projects, promoting interdisciplinary collaborations between R15-eligible and non-eligible U.S. domestic institutions, and engaging students in meaningful pain research experiences. Applicants must submit proposals that include rigorous research plans, interdisciplinary team management structures, and detailed strategies for involving students in research activities. Proposed projects must address diverse pain conditions, and clinical trials should focus on understanding pain mechanisms rather than evaluating treatment efficacy.

Funding for the program includes $1.25 million annually, supporting up to three awards per year in fiscal years 2026 and 2027. Applicants may request up to $375,000 in direct costs for projects lasting a maximum of three years. Eligible organizations include public and private higher education institutions with R15 eligibility, as defined by NIH funding levels and student population metrics. Collaborations with non-R15-eligible institutions are permitted, but the majority of research activities and budget allocations must occur at the R15-eligible institution.

Applications are subject to strict submission guidelines, including the requirement for a Plan for Enhancing Diverse Perspectives (PEDP), facilities and resources documentation, and collaboration letters. All applications must be submitted electronically via NIH’s ASSIST system or Grants.gov Workspace by the posted deadlines. Applicants are also encouraged to consult NIH program officers for guidance during the planning process.

Key dates include the earliest submission opening on September 29, 2025, with the first application deadline on October 28, 2025. Letters of intent, while optional, are due 30 days prior to the application deadline. The award timeline includes scientific merit review in March 2026, advisory council review in May 2026, and project start dates as early as July 2026.

Proposals will be evaluated based on scientific merit, feasibility, innovation, and the inclusion of diverse perspectives. Review criteria emphasize the significance of the research, the rigor of experimental approaches, the quality of student engagement plans, and the potential to strengthen institutional research environments. Successful applicants are required to attend NIH HEAL Initiative scientific meetings and adhere to HEAL data-sharing policies. For additional guidance, applicants may contact NIH representatives listed in the funding announcement.