NIH – HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes & Cells (U19 Clinical Trial Not Allowed)

February 11, 2022 by


The purpose of this funding opportunity announcement is to support research that uses human tissue or cells to generate comprehensive datasets for the discovery and characterization of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain transduction, transmission, and processing. This FOA will support concerted multidisciplinary team science efforts that apply large-scale high-throughput approaches on tissues involved in human pain processing as part of the NIH HEAL Initiative’s Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins, and the Nature of Human Pain (PRECISION Human Pain). U19 Centers will operate as a cooperative network to promote collaboration and coordination of research activities. U19 Centers will also coordinate with the U24 HEAL Initiative: Human Pain-associated Genes & Cells Data Coordination and Integration Center that will curate, harmonize, and integrate datasets generated by this U19 research program.


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:

The advent of single cell -omics and high throughput electrophysiologic technologies provide an immense opportunity to significantly expand currently available datasets concerning gene expression and cellular function of human pain processing cells and/or tissues. For example, several recent transcriptomic and single-cell functional studies utilizing primary neurons from human pain processing tissues; namely dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), and tibial nerves, have identified a number of potential genetic and cellular differences in human sensory neuron electrophysiologic signatures with translational implications. In addition, recent comparative transcriptomic studies of [whole] DRGs obtained from human subjects with or without pain conditions suggest several common genes associated with a small subset of neuropathic and cancer pain conditions. While promising, these data only begin to uncover the breadth of knowledge to be gained in this space and highlight the need to expand datasets to include heterogeneities across specific pain type/conditions comparing variables such as chronic analgesic or other drug use and co-morbid and/or overlapping pain conditions. It also highlights the need for standardization of methods, as approaches for tissue collection, processing, and analysis often vary across individual laboratories, thus posing a tremendous challenge for harmonized data collection, analysis, and reporting that would enable cross-comparison and rigorous validation.

To capitalize on recent technological advances in high throughput analyses of molecular, anatomic, and physiological measurements for single cell and tissue-level characterizations and address the increasing need to enhance data interoperability and harmonization among data producers, the NIH Heal Initiative has created the Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins and the Nature of Human Pain (PRECISION Human Pain). The PRECISION Human Pain network will be composed of a group of centers supported via two companion FOAs: the subject of this FOA is the U19 Centers for Discovery and Functional Evaluation of Human Pain-associated Genes & Cells. The companion FOA RFA-NS-22-021 will support a U24 Human Pain-associated Genes & Cells Data Coordination and Integration Center that will curate, harmonize, and integrate core datasets generated by the U19 Centers to generate digital resources.

Rapid progress in the discovery and understanding of the role of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain processing, as well as integrated data analysis and development of digital assets will require collaborations across disciplines. To effectively achieve the goals of the PRECISION Human Pain network and facilitate advances in pain research, the NIH HEAL Initiative encourages the formation of multidisciplinary research teams including neurobiologists, pain biologists, human pain scientists and/or physicians, and scientists from statistics, physics, mathematics, engineering, and computer and information sciences. NIH and the NIH HEAL Initiative also strongly encourage input from patients and caregivers on the scientific and research goals of this U19 research program.

In addition to scientific diversity, applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Please refer to Notice of NIH’s Interest in Diversity?NOT-OD-20-031?for more details.

The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities. In addition, it is expected that PRECISION Human Pain projects will work together, operating as a cooperative network to achieve its overall goals. This will include regular meetings and other coordinated activities within the PRECISION Human Pain network as well as the NIH HEAL Initiative, and the NIH more broadly. In particular, network Centers will work closely with the HEAL Data Ecosystem, which coordinates data sharing across the HEAL Initiative.

Key Dates:

Open: February 17, 2022
Letter of Intent Due Date(s): 30 days prior to the application due date
Earliest Application Due Date: March 17, 2022

URL for more information:

Filed Under: Funding Opportunities