Opportunity Information: Apply for PAR 27 045
The HEAL Initiative: Whole Joint Health Program (R61/R33 Clinical Trial Required) funding opportunity (PAR-27-045) is a National Institutes of Health (NIH) grant program under the broader Helping to End Addiction Long-term (HEAL) Initiative. Its central aim is to advance safer, non-addictive, and prevention-oriented solutions for chronic joint pain by funding clinical research that digs into the biological drivers of pain and then tests interventions designed to directly address those drivers. The program is framed around priorities highlighted during the 2023 HEAL Whole Joint Pain Workshop and aligns with broader federal goals to reduce reliance on addictive pain treatments by improving evidence for non-pharmacologic and multimodal care.
A key feature of this opportunity is its phased, milestone-driven structure using the R61/R33 mechanism, with a total project period of up to five years. The first phase (R61) focuses on identifying, characterizing, and validating understudied biological mechanisms that contribute to joint pain, specifically emphasizing multi-tissue mechanisms. This “whole joint” framing generally implies looking beyond a single tissue type to understand how different joint-related tissues and systems interact in producing pain. The second phase (R33) builds on the mechanistic findings and moves into testing clinical interventions that directly target those validated mechanisms. Importantly, this NOFO requires a clinical trial, meaning the funded work is expected to include prospective human research with intervention assignment and outcomes evaluation, rather than being purely observational or preclinical.
In practical terms, NIH is looking for research programs that do more than document symptoms or compare generic treatments. The expectation is that applicants will first produce convincing evidence that a specific mechanism (or a set of mechanisms) is meaningfully linked to joint pain and is measurable in humans, and then design non-pharmacologic or multimodal interventions that are intentionally chosen because they can influence those mechanisms. “Non-pharmacologic” typically covers approaches such as behavioral, physical, rehabilitative, neuromodulatory, device-based, lifestyle, and other non-drug strategies, while “multimodal” generally means combining approaches in a coordinated way. The program’s emphasis on mechanisms is meant to move the field toward targeted, biology-informed care rather than one-size-fits-all pain management.
Eligibility is broad across U.S.-based organization types and includes 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; certain tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding higher education institutions in those specific categories); for-profit organizations (other than small businesses); small businesses; and other eligible domestic entities as allowed under NIH rules. At the same time, this opportunity clearly limits international participation: non-U.S. (foreign) organizations are not eligible to apply, non-U.S. components of U.S. organizations are not eligible, and foreign components (as defined in the NIH Grants Policy Statement) are not allowed.
This is a discretionary grant program administered by NIH, listed under multiple CFDA/Assistance Listing numbers (93.121, 93.213, 93.273, 93.286, 93.473, 93.846, 93.853, 93.866), reflecting NIH’s multi-institute structure and the cross-cutting nature of pain research. The posted closing date is October 30, 2026. While the summary information provided does not specify an award ceiling or the expected number of awards, applicants should rely on the full NOFO details for budget guidance, review criteria, required milestones for the R61-to-R33 transition, and the specific scientific priorities NIH wants addressed.Apply for PAR 27 045
- The National Institutes of Health in the health sector is offering a public funding opportunity titled "HEAL Initiative: Whole Joint Health Program (R61/R33 Clinical Trial Required)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.213, 93.273, 93.286, 93.473, 93.846, 93.853, 93.866.
- This funding opportunity was created on 2026-09-28.
- Applicants must submit their applications by 2026-10-30. (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.
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Frequently Asked Questions (FAQs) - HEAL Initiative: Whole Joint Health Program (R61/R33 Clinical Trial Required) (PAR-27-045)
1) What is this funding opportunity?
This opportunity is the HEAL Initiative: Whole Joint Health Program (R61/R33 Clinical Trial Required) funding opportunity announcement (PAR-27-045) from the National Institutes of Health (NIH), under the broader Helping to End Addiction Long-term (HEAL) Initiative.
2) What is the overall goal of the program?
The central aim is to advance safer, non-addictive, and prevention-oriented solutions for chronic joint pain by funding clinical research that (1) investigates the biological drivers of pain and (2) tests interventions designed to directly address those drivers.
3) How does this relate to the HEAL Initiative?
This program is part of NIH's HEAL Initiative and aligns with broader federal goals to reduce reliance on addictive pain treatments by improving evidence for non-pharmacologic and multimodal care for pain.
4) What kind of research is NIH trying to support here?
NIH is looking for research programs that go beyond documenting symptoms or comparing generic treatments. The expectation is that applicants will identify and validate specific biological mechanisms meaningfully linked to joint pain (and measurable in humans), then test interventions intentionally selected because they can influence those mechanisms.
5) What does "Whole Joint" mean in this context?
The "whole joint" framing generally implies looking beyond a single tissue type and instead studying multi-tissue mechanisms to understand how different joint-related tissues and systems interact in producing pain.
6) What grant mechanism does this program use?
The program uses the NIH R61/R33 phased innovation award mechanism. It is milestone-driven and structured in two phases.
7) What is the maximum project period?
The total project period can be up to five years across both phases (R61 and R33).
8) What happens in the R61 phase?
The R61 phase focuses on identifying, characterizing, and validating understudied biological mechanisms that contribute to joint pain, with specific emphasis on multi-tissue ("whole joint") mechanisms.
9) What happens in the R33 phase?
The R33 phase builds on the mechanistic findings from R61 and moves into testing clinical interventions that directly target the validated mechanisms.
10) Is a clinical trial required?
Yes. This notice of funding opportunity requires a clinical trial, meaning funded work is expected to include prospective human research with intervention assignment and outcomes evaluation, rather than being purely observational or preclinical.
11) Does the program support observational-only studies?
Based on the information provided, the program is structured around a required clinical trial and is not described as supporting purely observational work without intervention assignment and outcomes evaluation.
12) What types of interventions fit this program?
The opportunity emphasizes non-pharmacologic and multimodal interventions that are deliberately chosen because they are expected to influence the validated biological mechanisms driving joint pain.
13) What does "non-pharmacologic" mean here?
"Non-pharmacologic" typically covers behavioral, physical, rehabilitative, neuromodulatory, device-based, lifestyle, and other non-drug strategies.
14) What does "multimodal" mean here?
"Multimodal" generally means combining approaches in a coordinated way, rather than relying on a single strategy.
15) What is meant by "biology-informed" or "mechanism-targeted" care?
In this program, it refers to moving away from one-size-fits-all pain management and toward targeted interventions selected because they address specific biological drivers of joint pain validated in humans.
16) What are "milestones" in the R61/R33 structure?
The program is described as milestone-driven, meaning progression from the R61 phase to the R33 phase depends on meeting defined milestones. Applicants should refer to the full NOFO for the required milestones and transition requirements.
17) Who is eligible to apply?
Eligibility is broad across U.S.-based organization types. Eligible applicants include: 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; certain tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding higher education institutions in those specific categories); for-profit organizations (other than small businesses); small businesses; and other eligible domestic entities as allowed under NIH rules.
18) Are foreign (non-U.S.) organizations eligible?
No. Non-U.S. (foreign) organizations are not eligible to apply.
19) Can a U.S. organization include a non-U.S. component?
No. Non-U.S. components of U.S. organizations are not eligible under this opportunity.
20) Are foreign components allowed at all?
No. Foreign components (as defined in the NIH Grants Policy Statement) are not allowed.
21) Which agency administers this grant?
This is a discretionary grant program administered by the National Institutes of Health (NIH).
22) What Assistance Listing (CFDA) numbers are associated with this opportunity?
The opportunity is listed under multiple Assistance Listing numbers: 93.121, 93.213, 93.273, 93.286, 93.473, 93.846, 93.853, and 93.866.
23) Why are there multiple Assistance Listing numbers?
The multiple listings reflect NIH's multi-institute structure and the cross-cutting nature of pain research described in the opportunity.
24) What is the application deadline or closing date?
The posted closing date is October 30, 2026.
25) Is there an award ceiling or a stated number of awards?
The summary information provided does not specify an award ceiling or the expected number of awards. Applicants are directed to rely on the full NOFO for budget guidance and related details.
26) Where should applicants look for budget guidance, review criteria, and required transition details?
Applicants should rely on the full NOFO details for budget guidance, review criteria, required milestones for the R61-to-R33 transition, and the specific scientific priorities NIH wants addressed.
27) What scientific priorities does this program align with?
The program is framed around priorities highlighted during the 2023 HEAL Whole Joint Pain Workshop and aligns with broader federal goals related to reducing reliance on addictive pain treatments.
28) What is the expected flow of work across the two phases?
The expected flow is: (1) produce convincing evidence in humans that a specific biological mechanism (or set of mechanisms) is meaningfully linked to joint pain and is measurable, then (2) test an intervention (non-pharmacologic or multimodal) that is explicitly designed to impact that mechanism.
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