NOT-NS-22-063: Notice of Intent to Publish a Funding Opportunity Announcement for HEAL Initiative: Human Pain-associated Genes & Cells Data Coordination and Integration Center (U24 Clinical Trial Not Allowed)

National Institute of Neurological Disorders and Stroke (NINDS)

The National Institutes of Health (NIH) intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications for multidisciplinary, team-based research efforts for the discovery and functional evaluation of human pain-associated genes and cells.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations among neurobiologists, pain biologists, human pain scientists and/or physicians, and scientists from statistics, physics, mathematics, engineering, and computer and information sciences. It will also allow potential applicants sufficient time to develop responsive projects. The FOA is expected to be published in Winter, 2022 with an expected application due date in Spring of 2022.

This FOA will utilize a multicomponent cooperative agreement mechanism (U19). Details of the planned FOA are provided below.

This funding announcement is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.

The NIH HEAL Initiative encourages research projects that aim to use human cells and tissues to accelerate the discovery and successful translation of pain therapeutics by supporting collaborative efforts to gain a better, more direct understanding of human pain-associated genes and functional elements that underly specific human pain types, conditions and/or diseases. Towards this end, the NIH HEAL Initiative has developed a Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins and the Nature of Human Pain (PRECISION Human Pain). PRECISION Human Pain will be comprised of a group of centers supported via two planned FOAs; one to support U19 Centers for the Discovery and Functional Evaluation of Human Pain-associated Genes & Cells, and another to support a U24 Human Pain-associated Genes & Cells Data Coordination and Integration Center (described in NOT-NS-22-063). It is expected that PRECISION Human Pain Centers will work together, operating as a cooperative network to achieve its key objectives.

The goal of the PRECISION Human Pain network is to use human cells and tissues to build up comprehensive datasets of molecular signatures, cell types, and cellular function phenotypes or signatures that underlie human pain signal transduction, transmission, and processing. Areas of interest infor this funding opportunity announcementt are not limited to specific pain types, conditions and/or diseases. Projects that propose to use human cells and tissues from multiple pain conditions in the context of chronic analgesic use, other drug use, substance use disorders (SUDs) and other co-morbid and/or overlapping pain conditions are encouraged.

Key objectives of the PRECISION Human Pain network will be to:

• Elucidate and validate functional roles of human genes and cellular phenotypes underpinning the heterogeneity, pathogenesis and susceptibility to specific pain conditions.
• Enable and accelerate the discovery and validation of condition/disease-specific human pain therapeutic targets with enhanced translational potential.

Research Objectives

The planned U19 Center FOA is designed to support multidisciplinary research teams to conduct highly collaborative and coordinated research utilizing cutting-edge technologies and approaches to generate comprehensive datasets from primary human tissues involved in pain processing, including but not limited to dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), sympathetic ganglia (SG), brainstem, brain, peripheral nerve bundles/fibers, and skin. Required Center components will include an Administrative Core, a Tissue Procurement and Processing Core, a Data Core, and up to three Research Projects. Optional Resource Cores to support the Center may also be included. Center components should be integrated and create synergy to achieve its overall goals.

Research Projects will focus on large-scale, high-throughput analyses of human genes, epigenetic elements, proteome, metabolome, and phenotyping of neuronal and non-neuronal cells at the single-cell and tissue levels, as well as their functional crosstalk that leads to the hyper/hypo-activation of sensory neurons within the context of individual pain types, pain conditions and/or diseases.

U19 Centers will work closely with the planned U24 Data Coordination and Integration Center to adopt and promote standard terminology, data acquisition protocols, quality control metrics, and metadata requirements to enhance data interoperability and harmonization across the network and the broader research community. U19 Centers will also coordinate with the Data Coordination and Integration Center in its efforts to curate, harmonize, and integrate U19 Center-generated datasets.

It is expected that PRECISION Human Pain network centers will work closely with the NIH HEAL Initiative’s Public Access and Data Ecosystem (https://heal.nih.gov/about/public-access-data), to maximize sharing and dissemination of datasets and digital assets to the pain research and therapeutics development communities.

The comprehensive -omics and cellular function datasets generated from PRECISION Human Pain network will significantly accelerate first-hand validation of pain therapeutic targets in human pain-relevant cells and tissue. These studies will also facilitate the identification and development of potential markers that reflect target engagement, thus providing valuable assets for translational research and therapeutic development. In all, the integrated datasets and digital resources developed through this initiative will be highly informative for multiple ongoing and future pre-clinical and translational programs in the NIH HEAL initiative and the NIH more broadly.

Applicants are strongly encouraged to consult with NIH program staff as plans for an application are being developed.