HEAL Initiative: Understanding Individual Differences in Human Pain Conditions (R01 - Clinical Trial Optional) | RFA NS 25 020

Opportunity Information: Apply for RFA NS 25 020

The HEAL Initiative: Understanding Individual Differences in Human Pain Conditions (R01 - Clinical Trial Optional) funding opportunity (RFA-NS-25-020) is a National Institutes of Health (NIH) grant aimed at improving how pain is understood and treated by focusing on why pain differs so much from one person to another. The central emphasis is on a Whole Person Health perspective, meaning applicants are expected to look beyond a single biological marker or single diagnosis and instead examine the broader mix of factors that shape pain experiences and outcomes across individuals. The overall intent is to generate knowledge that can move the field toward personalized or precision pain medicine, where prevention, treatment selection, and management strategies can be tailored to distinct subgroups of people with pain rather than relying on one-size-fits-all approaches.

A key goal of the NOFO is to support studies that collect clinical and/or preclinical data specifically suited to building evidence-based models of pain heterogeneity. In practice, this means the research should be designed to capture and explain between-person differences in pain conditions, including differences in severity, persistence, functional impact, treatment response, and the way pain changes over time. The NOFO particularly encourages work that examines pain in the context of pain therapy or pain management (for example, why individuals respond differently to the same intervention), as well as pain that occurs alongside other real-world complexities such as having a second pain condition, a comorbid physical health condition, a comorbid mental health condition, or patterns of substance use or misuse involving opioids, alcohol, or other substances. The underlying expectation is that studies will yield interpretable, data-driven insights about mechanisms and profiles that distinguish subgroups of patients, rather than simply describing average effects.

The opportunity also places strong emphasis on rigorous, multidisciplinary approaches. NIH is signaling that the complexity of inter-individual pain differences will require teams with complementary expertise, which may include (depending on the project) pain medicine, neurology, anesthesiology, psychiatry, psychology, behavioral science, epidemiology, biostatistics, computational modeling, informatics, and other relevant disciplines. The NOFO calls for novel approaches where appropriate, and for study designs that can support robust stratification of participants with lived pain experience. The types of insights sought span biological and biopsychosocial underpinnings, reflecting the idea that pain variation often comes from interactions among nervous system processes, immune and endocrine factors, mental health, environment, stress, sleep, trauma history, social determinants, and treatment exposures. Clinical trials are optional under this R01 mechanism, so applicants can propose either observational or interventional work as long as it fits the purpose of understanding and modeling individual differences in pain.

Patient and caregiver engagement is explicitly encouraged. Rather than treating patient input as an afterthought, the NOFO highlights the value of incorporating perspectives from people living with pain and those who support them when shaping research goals, outcomes of interest, and practical relevance. This aligns with the broader Whole Person Health framing and increases the likelihood that results will translate into care decisions that matter to patients, such as improved function, quality of life, and reduced harms from ineffective treatments or inappropriate medication use.

From an administrative standpoint, this is a discretionary NIH grant using the R01 funding instrument, listed under multiple CFDA numbers (93.213, 93.233, 93.279, 93.395, 93.837, 93.838, 93.839, 93.840, 93.846, 93.853, 93.865, 93.866, 93.867), reflecting the multi-institute nature of pain-related research within NIH and HEAL priorities. The opportunity was created on 2024-10-08, with an original closing date of 2025-02-06. An award ceiling is not specified in the provided listing, and the expected number of awards is not stated there, so applicants should plan budgets consistent with R01 norms and the scope of work proposed, while checking the full NOFO for any institute-specific limits or expectations.

Eligibility is broad and includes many common applicant categories such as state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized governments); public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. The NOFO also highlights additional eligible applicant types, including Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); eligible federal agencies; faith-based or community-based organizations; U.S. territories or possessions; regional organizations; and non-domestic (non-U.S.) entities (foreign organizations). This broad eligibility underscores the intention to draw from diverse research environments and encourage participation by institutions that serve populations often underrepresented in biomedical research, which is especially relevant when studying heterogeneity in pain experiences and treatment outcomes.

In short, this HEAL Initiative NOFO is designed to fund strong, data-rich, team-based studies that explain why pain and pain treatment outcomes vary across people, especially in the presence of comorbidities and substance use factors, and to turn that understanding into clearer stratification and modeling that can speed progress toward precision pain care.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "HEAL Initiative: Understanding Individual Differences in Human Pain Conditions (R01 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213, 93.233, 93.279, 93.395, 93.837, 93.838, 93.839, 93.840, 93.846, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2024-10-08.
• Applicants must submit their applications by 2025-02-06. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA NS 25 020

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