NIH – Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01, R21 Clinical Trial Not Allowed)

October 1, 2018 by School of Medicine Webmaster

The following description was taken from the R01 version of this FOA.

The purpose of this Funding Opportunity Announcement (FOA) is to promote the discovery and validation of novel therapeutic targets to facilitate the development of pain therapeutics.  Specifically, the focus of this FOA is on the basic science discovery of targets in the peripheral nervous system, central nervous system, immune system or other tissues in the body that can be used to develop treatments that have minimal side effects and little to no abuse/addiction liability. Research supported by this FOA must include rigorous validation studies to demonstrate the robustness of the target as a pain treatment target. This will lower the risk of adopting the target in translational projects to develop small molecules, biologics, natural substances, or devices that interact with this target for new pain treatments. Translational research to develop new medical devices is not the focus of this FOA. Basic science studies of pain and related systems in the body are responsive to this FOA and are encouraged in the context of novel pain therapeutic target discovery.

This FOA is not specific for any one or group of pain conditions. Projects to identify novel targets for acute pain, chronic pain, migraine, other headache disorders, osteoarthritis, diabetic neuropathy, chemotherapy-induced neuropathy, sickle-cell pain, post stroke pain, etc. will be considered. Projects to identify novel targets for a combination of chronic overlapping pain conditions or for specific pathological conditions will be considered. Projects that seek to identify novel targets in specific populations such as women, children, older adults or other underrepresented groups will also be responsive to this FOA.


This study 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 will bolster 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: .

More than 25 million Americans suffer from daily chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an overreliance in the prescription of opioids for chronic pain despite their poor ability to improve function. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative treatment options are thus critically needed.

The development of nonaddictive therapeutics for the treatment of pain requires the discovery of new targets for the treatment of acute and chronic pain. Once identified, pain treatment targets require rigorous validation to justify the significant investment in therapeutic development. Rigorous approaches to target validation include the use of multiple approaches, such as the validation of targets in animal models, human tissue, and/or validation of key experiments in other laboratories.

The goal of this funding opportunity announcement is to encourage applications to identify novel nonaddictive pain targets that include rigorous target validation studies. These studies should have the goal of definitively determining the utility of a potential target for future therapeutic development.

Matching Requirement:

As part of the HEAL Initiative, this FOA is subject to certain requirements for for-profit applicant organizations. Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.

A grantee from a for-profit organization funded under this funding opportunity announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award.  NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement.  See 45 CFR 75.306 for additional details.

Research Objectives

  • Applications to this FOA must propose a research plan designed to discover and validate a novel target or to validate an existing target for pain treatment with little to no abuse liability.
  • Applications to identify targets for devices, such as peripheral nerve, spinal cord, or deep brain stimulators may focus on identifying electrophysiological signatures for acute or chronic pain. Validation of these targets in large animals or nonhuman primates should be considered.
  • Experiments to demonstrate a lack of abuse liability of the target should be considered.
  • Early pain therapeutic target discovery projects are responsive to this FOA, but they must include a plan for validating the target once it is identified.
  • In addition to discovery projects to identify pain therapeutic targets for small molecules, pain therapeutic targets for biologics, such as antibody or cell-based therapies, are encouraged.
  • Applications focused on target validation alone will be considered responsive. Applications focused on target discovery alone should submit to PA-18-141 instead.
  • Scientific rationale: Projects should be supported by a cogent biological rationale. Applicants should also discuss how the experimental approach will lead to a novel target.
  • Validation: Projects must include a plan for rigorously validating the target using multiple animal models, reproducing the work in another laboratory, or in human tissue etc.
  • Relevance for pain therapeutic development: Projects should address the relevance of the target for subsequent pain therapy development.

Examples of studies that are NOT responsive for this FOA

  • Natural history studies aimed at understanding disease pathophysiology, genetic, or epigenetic mechanisms in the absence of target discovery identification, development and validation
  • Large, prospective design clinical validation studies
  • Prospective design clinical utility studies
  • Preclinical animal studies focused only on therapeutic development (see PAR-18-761:
  • Development of candidate therapeutics (see
  • Clinical trials to optimize dosing or timing of therapeutic intervention, studies to inform stratification of human subjects, or studies designed to test efficacy in human subjects.
  • Technical development of neurostimulation or other medical devices for the treatment of pain


Investigators are encouraged to form collaborations with individuals knowledgeable in bioinformatics, statistical analysis, pain biology and physiology, clinical experience appropriate for the type of pain treatment discovery, as well as those familiar with the ultimate goal of a successful project for this FOA, which is to have a robust candidate target for nonaddictive therapeutics development.

Leveraging Existing Research Resources

Applicants are strongly encouraged to leverage existing research resources for their studies whenever possible. Such resources may include tissue, cellular, or DNA samples from NINDS BioSEND or other existing biospecimen, imaging and data repositories. The NINDS BioSEND repository receives, processes, stores, and distributes biospecimen resources from NINDS funded studies that can be shared by the neuroscience research community, and currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva. Leveraging the resources and support from pain advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program is also encouraged. Studies are also encouraged that leverage the resources of ongoing clinical trials supported through other Federal or private funds.

Applicants are encouraged to utilize the state-of-the-art capabilities at the NIH National Center for Advancing Translational Sciences (NIH/NCATS) in support HEAL initiatives.  A detailed description of the capabilities can be found at:

Pre-Application Consultation 

Applicants are strongly encouraged to consult with NINDS Scientific/Research Staff early on during the planning for an application. This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope of project relative to the HEAL initiative mission and intent of this FOA.

NIH Institute and Center Interests and Guidance

The National Institute of Dental and Craniofacial Research (NIDCR) is interested in the discovery and validation of novel therapeutic targets to facilitate development of therapeutics for painful disorders of the orofacial region including temporomandibular joint disorders, trigeminal neuropathies, burning mouth syndrome, oral cancer pain, dental pain, and other conditions. Investigators are encouraged to contact NIDCR program staff to discuss potential research projects prior to application submission to determine alignment of the planned studies with priorities of the Institute mission and strategic plan.

Deadlines:  November 27, 2018; February 11, 2019; July 11, 2019; November 12, 2019 (letters of intent due 30 days prior to the application deadline)


Filed Under: Funding Opportunities