Initiative: Studies to Enable Analgesic Discovery (R61/R33 – Clinical Trial Not Allowed)
🏛 National Institutes of Health (HHS-NIH11)
✓ Free, no account · Source: Grants.gov · Last verified Jul 16, 2026
Can you apply?
This grant is for researchers and research institutions seeking to fund innovative studies aimed at enabling new pain management drug discovery and development, without conducting clinical trials. The R61/R33 mechanism is designed for early-stage projects that will advance analgesic development. Eligible applicants typically include academic medical centers, research institutions, nonprofits, and other entities with active research capacity. Proposals must demonstrate novel approaches to pain relief and mechanisms that could lead to new therapeutic options. This is a national program, and geographic scope is not restricted. The funding supports research activities, exploratory work, and transition from proof-of-concept to development-stage research, but excludes direct clinical trial implementation.
Not the right fit? Find grants for your organization in 5 questions →
Program description
This funding opportunity is part of a suite of NOFOs within the NIH HEAL Initiative to support the development of safe, effective, and non-addictive therapeutics to treat pain. The goal is to encourage initial translational efforts that will support a drug discovery program and advance projects to the point where they meet the entry criteria for the Pain Therapeutics Development Program. The scope will therefore be focused on development of assays to support a distinct testing funnel, screening efforts to identify hits, and initial characterization of hits and potential therapeutic agents (including small molecules, biologics, and natural products).
Who can apply
Eligible applicants
How to apply
Application links
Required documents
- NIH Form SF-424 (R&R)
- Project Narrative (research strategy) with specific aims, background, significance, innovation, and approach
- Preliminary Results/Proof-of-Concept data (R61 phase)
- Detailed R61 and R33 milestone definitions and go/no-go criteria
- Budget and budget justification (including facilities and administrative costs)
- Biographical sketches of key personnel (NIH format)
- Letters of support and institutional commitment
- Description of institutional resources and research environment
- Data sharing and management plan
- NIH-required compliance certifications (IRB, IACUC if applicable, conflict of interest)
Program contact
- 👤 National Institutes of Health
- 📧 grantsinfo@nih.gov
- 📞 301-402-2541
Funding track record
Recent awards under CFDA 93.846 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$63,962,483
-
$60,038,896
-
$34,166,872
-
$27,648,731
-
$24,598,295
-
$21,654,386
-
$20,225,012
-
$16,326,540
-
$15,274,546
-
$14,828,008
Top States by Funding
- CA 13 awards $124.1M
- MA 15 awards $123.0M
- NY 12 awards $107.4M
- NC 4 awards $102.5M
- PA 11 awards $101.4M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.846). How funding has trended year over year.
| 2018 | $476,478,975 | |
| 2019 | $490,084,446 | |
| 2020 | $505,547,334 | |
| 2021 | $509,241,630 | |
| 2022 | $499,786,367 | |
| 2023 | $548,439,000 | |
| 2024 est. | $545,593,000 | |
| 2025 est. | $541,712,000 |
FAQ
Who is eligible to apply for this HEAL Initiative grant?
Research institutions including academic medical centers, nonprofits, government agencies, and small businesses with established research capacity and appropriate facilities. Applicants typically need institutional research infrastructure and compliance systems.
What is the R61/R33 mechanism?
A two-phase funding structure: R61 (exploratory phase, typically 1-2 years) focuses on proof-of-concept; R33 (development phase, typically 2 years) supports scale-up and further validation. Transition between phases is contingent on achieving specific milestones.
What types of research activities are supported?
Studies focused on analgesic drug discovery, mechanism of action research, target identification, and preclinical development. Clinical trials are explicitly not allowed under this mechanism.
When is the deadline?
The fixed deadline is January 15, 2027. Applications typically open several months prior; check NIH grants.gov for specific submission windows and any LOI requirements.
How competitive is this funding?
NIH grants are highly competitive with success rates typically in the 15-25% range. Strong preliminary data, clear innovation, experienced research teams, and specific aims are essential.
💡 Tips for applicants
- Demonstrate clear, significant innovation in analgesic discovery—explain what makes your approach novel compared to existing methods and previous NIH-funded work in this area.
- Build strong preliminary data in your R61 phase proposal; reviewers will scrutinize proof-of-concept and the feasibility of transition milestones to R33 funding.
- Clearly articulate specific, measurable milestones for the R61 phase and explain how achievement of these milestones will justify R33 continuation, including quantitative go/no-go criteria.
- Avoid proposing clinical trials or human subject research; focus entirely on discovery and preclinical/laboratory-based development to align with the "Clinical Trial Not Allowed" restriction.
- Address pain biology and therapeutic gaps directly—connect your research to unmet clinical needs in pain management and explain the public health significance of your approach.
⚠️ Common mistakes
Applicants often fail to distinguish between exploratory R61 work and development-phase R33 goals, resulting in unclear or overly ambitious transition milestones. Many proposals underestimate the need for robust preliminary data in the R61 phase or propose clinical trial components that violate the mechanism restrictions. Additionally, weak justification of how the analgesic target or mechanism represents a genuine therapeutic advance—rather than incremental improvement—frequently leads to dismissal during review.
Similar grants
- OPEN HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional) — National Institutes of Health
- OPEN HEAL Initiative: Pain Research Enhancement Program (PREP) (R15 Clinical Trial Optional) — National Institutes of Health
- CLOSED HEAL Initiative-Early-Stage Discovery of New Pain Targets Within the Understudied Druggable Proteome (R03 Clinical Trial Not Allowed) — National Institutes of Health
- CLOSED HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required) — National Institutes of Health
- OPEN HEAL Initiative: Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins and the Nature of (PRECISION) Human Pain Network — National Institutes of Health