Exploring Epigenomic or Non-Coding RNA Regulation in the Development, Maintenance, or Treatment of Chronic Pain (R61/R33 Clinical Trial Optional) | PAR 18 742

Opportunity Information: Apply for PAR 18 742

This NIH grant opportunity (PAR 18-742) supports research aimed at understanding how epigenomic mechanisms and non-coding RNA pathways influence the development, persistence, and potential treatment of chronic pain. The core idea is to push the field beyond symptom management and toward the biological control systems that can lock pain into a chronic state. By clarifying how gene activity is regulated without changing the underlying DNA sequence, or how non-coding RNAs fine-tune cellular behavior, projects funded under this announcement are expected to generate foundational insights that could eventually be translated into new, non-addictive pain therapies.

The scientific focus is on molecular regulation, specifically epigenetic regulation (for example, DNA methylation, histone modification, chromatin remodeling, and other mechanisms that change how accessible genes are to be turned on or off) and regulation mediated by non-coding RNAs (such as microRNAs, long non-coding RNAs, and other RNA species that shape gene expression and cellular signaling). The opportunity is framed around chronic pain broadly, emphasizing the need to understand both how chronic pain begins and how it is maintained over time. Research can be oriented toward mechanisms in relevant tissues and systems involved in pain processing and persistence, including peripheral and central nervous system pathways as well as immune and inflammatory components, as long as the work is tightly centered on epigenomic or non-coding RNA regulation in chronic pain.

The funding mechanism is the R61/R33 phased innovation award, and clinical trials are optional. In practice, that structure is designed for projects that need an initial, milestone-driven “early phase” to establish feasibility or generate decisive preliminary evidence (R61), followed by a second phase to expand, validate, or advance the work once those milestones are met (R33). This format fits research programs where the first stage might involve developing or validating a model, assay, dataset, or mechanistic hypothesis, and the second stage builds on that foundation to deepen mechanistic understanding or move toward translational applications. Although the notice allows clinical trials, it does not require them, meaning applicants can propose basic, translational, or clinically oriented studies as long as they match the program’s intent and satisfy NIH requirements for human subjects research when relevant.

Eligibility is broad and includes many types of organizations. Eligible applicants include state, county, city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofit organizations (both with and without 501(c)(3) status, as long as they are not institutions of higher education when applying under those categories); for-profit organizations (other than small businesses); small businesses; public housing authorities/Indian housing authorities; and Native American tribal governments (federally recognized) as well as Native American tribal organizations that are not federally recognized tribal governments. The announcement also explicitly highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions; Asian American, Native American, and Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); faith-based or community-based organizations; eligible federal agencies; regional organizations; U.S. territories or possessions; tribal governments that are not federally recognized; and non-U.S. entities (foreign organizations), indicating an intent to encourage wide participation, including underserved and international research communities where appropriate.

Administratively, the opportunity is a discretionary grant run by the National Institutes of Health, listed under CFDA numbers 93.213 and 93.279. The original closing date provided in the source information is February 11, 2021, and the notice was created on April 3, 2018. The source data does not specify an award ceiling or the expected number of awards, so applicants would typically look to the full funding announcement and related NIH institute guidance for budget expectations, project period norms under the R61/R33 mechanism, and any institute-specific priorities tied to chronic pain research.

Overall, the program is meant to accelerate a particular slice of pain research: identifying and validating epigenomic and non-coding RNA control points that help explain why pain becomes chronic and how it might be reversed or better managed without relying on addictive medications. The emphasis on regulatory biology signals an interest in targets and pathways that could be modulated to change pain states more durably, potentially enabling new classes of therapeutics, biomarkers, or intervention strategies grounded in gene regulation rather than traditional analgesic approaches.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Exploring Epigenomic or Non-Coding RNA Regulation in the Development, Maintenance, or Treatment of Chronic Pain (R61/R33 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, 93.279.
• This funding opportunity was created on 2018-04-03.
• Applicants must submit their applications by 2021-02-11. (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 PAR 18 742

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