HEAL Initiative Notice of Special Interest (NOSI): Development and Validation of Pain-Related Models and Endpoints to Facilitate Non-Addictive Analgesic Discovery
Notice Number:

Key Dates

Release Date:

July 14, 2022

First Available Due Date:
October 18, 2022
Expiration Date:
June 25, 2025

Related Announcements

PAR-21-123: Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Development and Validation of Model Systems to Facilitate Neurotherapeutic Discovery (R61/R33 Clinical Trial Not Allowed)

Issued by

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)


The purpose of this Notice of Special Interest (NOSI) is to encourage the development, validation, and replication of animal models that recapitulate the phenotypic and physiologic characteristics of a defined pain type/indication and/or disease-associated pain condition and endpoints or outcome measures that can be used therein. The goal of this NOSI is to improve the translational application of animal models and/or outcome measures for the development of non-addictive analgesics. Ideally, models or measures proposed for this NOSI would have the potential to provide feasible and meaningful assessments of efficacy following therapeutic intervention that would be applicable in both preclinical and clinical settings.

This NOSI is not specific for any one or group of pain conditions. Projects focused on acute pain, chronic pain, painful neuropathy, musculoskeletal pain, headache disorders, osteoarthritis, diabetic neuropathy, chemotherapy-induced neuropathy, eye pain, sickle-cell pain, post-surgical pain, cancer pain, visceral pain, obstetric pain, gynecologic pain, post stroke pain, myofascial pain, painful disorders of the orofacial region, pain co-occuring with substance use disorders, and other conditions will be considered. In addition to replication and validation of more commonly used translational animal models of pain, the development of animal models of pain for understudied pain conditions, age groups or less developed models is also encouraged.


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/.

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 on the prescription of opioids for chronic pain despite their poor ability to improve function and high addiction liability. This contributed to a significant and alarming epidemic of opioid addictions and overdose deaths. Innovative scientific solutions to develop alternative pain treatments are critically needed.

Therapeutics development relies on preclinical efficacy evaluation in animal models of disease; thus, it is critical that models and outcome measures/endpoints represent causally relevant aspects of pain pathology and are well-validated in terms of their predictive relationship to clinical outcomes. This initiative encourages rigorous internal and external validation studies of models, outcome measures and endpoints. External validation refers to the demonstration that the model can recapitulate aspects of the disease phenotype and etiology (see PAR-21-123 for details regarding external validation, including face, construct, and predictive types of validity). Validation may also include independent replication studies, ideally at multiple sites. Validation studies that include independent replication would lend greater confidence in the model and/or endpoint(s) by the broader research community, and use of these well-validated models and endpoints in the evaluation of candidate therapeutics has the potential to increase reproducibility, ultimately de-risking translational projects.

Research Objectives

This NOSI will support the development, validation, and independent replication of translationally relevant animal models, endpoints, and outcome measures for pain using PAR-21-123.
Applications to this NOSI must address all requirements of PAR-21-123.

Validation studies are required under PAR-21-123. As part of the larger validation plan, projects may include independent replication studies, including replication studies carried out by partnering academic institutions, contract research organizations, and/or small business concerns. Proposals focused solely on replication studies of preexisting models are allowed; applications may also expand variables as appropriate (e.g., testing across different ages, incorporating relevant comorbities, multiple endpoints, etc.).

A current challenge in the field is that interventions showing efficacy in animal models of pain often fail to produce significant clinical outcomes in humans. Therefore, applications are strongly encouraged to focus on models that reflect human pathological pain and promote a significant improvement in the translational relevance of animal models that will be utilized to facilitate future development of non-addictive analgesics.

Resources are available for applicants looking to maximize the impact of their HEAL-supported projects through broad data sharing. Information on HEAL Data Stewardship can be found here: https://www.healdatafair.org/

Examples of applications or studies that are non-responsive to this NOSI:

  • Applications for animal models/endpoints/outcome measures not focused on pain indications and/or conditions
  • Applications focused on the development and validation of in vitro or ex vivo model systems
  • Applications that include studies aimed at evaluating a potential therapeutic agent for efficacy or safety

Interested investigators are strongly encouraged to contact Scientific/Research staff prior to submitting an application.

Application and Submission Information

This notice applies to due dates on or after October 18, 2022 and subsequent receipt dates through June 25, 2025. 

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

  • PAR-21-123 - Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Development and Validation of Model Systems to Facilitate Neurotherapeutic Discovery (R61/R33 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-NS-22-095” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Rebecca Roof, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: rebecca.roof@nih.gov

Julia L Bachman, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Email: julia.bachman@nih.gov

Alex Tuttle, PhD
National Center for Complimentary and Integrative Health (NCCIH)
Telephone: 301-814-6115
Email: alex.tuttle@nih.gov

Mark Egli, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Email: megli@willco.niaaa.nih.gov

Melissa Ghim, PhD
National Institute Of Dental & Craniofacial Research (NIDCR)
Telephone: 301-529-6570
E-mail: melissa.ghim@nih.gov

Rachel Altshuler, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5873
Email: rachel.altshuler@nih.gov

Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350

Helena Ahn, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-3207
Email: helena.ahn@nih.gov

Marie Mancini, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: mancinim2@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov