The National Institutes of Health (NIH) invites applications for the HEAL Initiative-Early-Stage Discovery of New Pain Targets Within the Understudied Druggable Proteome program, under the R03 small grant mechanism. This funding opportunity supports pilot projects to identify and characterize new druggable targets for pain from a specific list of **understudied proteins** within the druggable proteome (DP). The primary objective is to jumpstart research on these proteins to generate preliminary data and/or tools that will advance understanding of their biological function in the context of pain and pain management. This initiative is part of the NIH HEAL Initiative, which aims to accelerate solutions to the national opioid crisis by improving pain treatment and reducing addiction.

The eligible proteins for study fall within defined protein families, including ion channels, transcription factors, transporters, proteases, and G-protein coupled receptors (GPCRs). Each protein listed has been designated as understudied due to limited research activity, such as low PubMed citation counts and minimal prior funding. Applications must focus exclusively on one or more proteins from the eligible list. Studies on proteins not on this list will be deemed non-responsive and returned without review. Responsive projects should aim to uncover the function, signaling pathways, structure-activity relationships, or therapeutic potential of these proteins in pain models, supporting future drug discovery or grant applications.

This funding opportunity encourages various types of small, self-contained projects that can be completed within one year with limited funding. Examples include feasibility studies, basic biochemical characterization of proteins, preclinical studies in animal models, and the development of tools such as assays or cell-based models to study protein function. Projects must not include clinical trials or focus on diseases unrelated to pain or pain management. Applications are also expected to contribute to the HEAL Initiative Data Ecosystem by adhering to specific data sharing and metadata submission requirements.

Applicants from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women, are encouraged to apply. NIH emphasizes the importance of diversity in scientific research to promote innovation, address health disparities, and enhance public trust. Award recipients will be required to participate in annual HEAL Investigators Meetings and share their research findings with the broader HEAL research community.

Applicants are limited to a maximum of **$100,000 in direct costs** for a project period of **one year**. Applications are due on standard NIH due dates beginning February 16, 2025, and continuing through June 16, 2026. Potential applicants should carefully review NIH submission requirements and ensure all registrations, including SAM.gov, eRA Commons, and Grants.gov, are completed well before the deadline.

Eligible applicants include higher education institutions, nonprofits, small businesses, local governments, and federally recognized Native American tribes. Non-domestic entities are not eligible, though foreign components of U.S. organizations are allowed. Applications will be evaluated on their significance, innovation, rigor, and feasibility, as well as the expertise of the research team and the adequacy of institutional resources. Projects must clearly justify the selected protein(s) and propose approaches that will enable further characterization in pain-related contexts.

Applications must be submitted electronically through Grants.gov or NIH ASSIST. For assistance, applicants are encouraged to contact NIH program staff listed in the funding announcement. Successful awardees will need to comply with HEAL’s public access, data sharing, and reporting requirements, ensuring that results are accessible to the broader scientific community and align with NIH’s commitment to open data and immediate publication access.