IPRCC Meeting - November 22, 2021

National Institutes of Health

Conference Call

10:00am - 3:30pm ET

Federal Register Notice

Interagency Pain Research Coordinating Committee

November 22, 2021

Virtual Meeting

Welcome and Introductions

On November 22, 2021, at 10:00 a.m., the Interagency Pain Research Coordinating Committee (IPRCC) convened for a virtual meeting. In accordance with Public Law 92-463, the meeting was open to the public. Walter Koroshetz, MD, Director of the National Institute of Neurological Disorders and Stroke (NINDS), and Helene Langevin, MD, Director of the National Center for Complementary and Integrative Health (NCCIH), presided as co-chairs.

The following IPRCC members were in attendance:

  • Federal Members: Charles G. Helmick, II, MD; Elisabeth Kato, MD; Walter Koroshetz, MD; Rigoberto Roca, MD; Friedhelm Sandbrink, MD
  • Scientific Members: Daniel B. Carr, MD; Beth Darnall, PhD; Christine Goertz, DC, PhD; Robert D. Kerns, PhD; Jose Moron-Concepcion, PhD; Christine Nai-Mei Sang, MD, MPH; David A. Williams, PhD; Todd Vanderah, PhD
  • Public Members: Maggie Buckley; Julie Eller; Katherine Hammitt; Gwenn Herman; Lynne Matallana; Sue Pinkham; Irma Rodriguez
  • Ex-Officio Members: Rena D’Souza, DDS, PhD; Helene Langevin, MD
  • Designated Federal Official: Linda L. Porter, PhD

What If? 2022 Pending NIH Budget for Pain Research: HEAL and Trans-NIH Allocations

Walter Koroshetz, MD, Director, NINDS

As of this meeting, the National Institutes of Health (NIH) and the entire U.S. government are operating on a Continuing Resolution and thus under 2021 budgets. However, 2022 budget proposals by both Congress and the President increase allocations specific to pain research ($616 million and $627 million, respectively). The earliest passage of a final budget for 2022 is expected to occur in March. Given typical grant cycles, IPRCC, NIH Institutes and Centers (ICs), and the Helping to End Addiction Long-term (HEAL) Initiative should plan for fund disbursement ahead of allocation.  

Funds allocated to ICs can be used for both IC-specific goals and for collaborative endeavors. The anticipated 2022 funds provide more opportunities for basic pain research than prior year funds, which were directed more toward translational research and through the HEAL Initiative. This new flexibility enables an IC to fund innovative projects related to pain in the context of its mission. In the coming months, the IPRCC will build on the discussions that occurred during this meeting regarding the optimal disbursement of anticipated pain research funding. The messaging surrounding this funding must capture this freedom without overpromising funding availability and must also communicate the ambiguity surrounding funding timelines.

Highlighted New HEAL Programs Awarded in 2021

HEAL Community Partnership Committee

Linda Porter, PhD, Director, Office of Pain Policy, NINDS

The recently established HEAL Community Partnership Committee (HCPC) consists of patients, advocates, liaisons, and family members who provide input to HEAL on key issues faced by individuals affected by both pain and addiction. HCPC enables HEAL to incorporate stakeholders in its governance structure by operating in an advisory capacity beneath the HEAL Partnership Committee, the Multi-Disciplinary Working Group (MDWG), and the HEAL Executive Committee. The NIH Patient Engagement WG, which represents people with lived experience in clinical trials, also works directly with HCPC to achieve mutual goals. In addition, HCPC supports HEAL investigators by providing resources to engage stakeholders and improve the recruitment, retention, and inclusion of underrepresented minorities in their study teams. For example, to assist investigators in increasing stakeholder engagement, HCPC provided a patient engagement survey to establish the baseline of HEAL awardee activities, emphasizing patient and community engagement, diversity, and inclusion. Furthermore, HCPC conducted focus groups informed by survey data to facilitate collaborations across investigative teams to enhance community engagement approaches.


No plan currently exists to publish findings from focus groups that would facilitate the adoption of best practices for stakeholder engagement by HEAL applicants. However, developing such a plan is a high priority for IPRCC and will be the subject of an update at the next IPRCC meeting.

Some research groups have extensive connections with people with lived experience and other clinical partners; for example, researchers within the Veteran’s Health Administration partner with groups of patients at the start of research projects when key research questions are developed. HEAL currently offers assistance with patient engagement only to HEAL-funded investigators; however, it may invest in developing this capacity for investigators more broadly, perhaps by supporting creation of patient panels at the institutional level.

Increasing Participant Diversity, Inclusion and Engagement in Clinical Studies (NOT-NS-21-025)

Cheryse Sankar, PhD, NINDS

HEAL seeks to address the separate but related challenges of patient engagement and diversity and inclusivity among study participants. Therefore, HEAL published a Notice of Special Interest (NOSI) titled “Availability of Administrative Supplements for Ongoing Clinical Studies that Support Strategies for Increasing Participant Diversity, Inclusion, and Engagement in Clinical Studies” (NOT-NS-21-025), to provide an opportunity for HEAL-funded studies to address the challenges of recruitment, retention, inclusion, or engagement of populations suffering from pain and opioid use disorder (OUD), with a particular emphasis on participants from racial and ethnic minority populations. This supplement is designed to increase the generalizability of study findings across the U.S. population, thereby decreasing the risk of perpetuating or even increasing health disparities.

The full spectrum of HEAL studies were represented among the 14 applications submitted for this supplement, spanning research on OUD treatment and prevention, specific pain conditions, and chronic pain (CP) broadly. The studies used a variety of approaches to increase stakeholder diversity, inclusion, and engagement, including establishing and diversifying stakeholder advisory boards and patient focus groups, producing culturally tailored recruitment materials, employing translation services, and using patient liaisons. In addition, some studies developed innovative methods for patient engagement. For example, one personalized approach uses a Patient-Centered Outcomes Research Institute story booth to collect information from patients about their experiences with pain and study participation. Another innovative method employs a data-driven tool to determine participants at risk for loss to follow-up, which enables a recruitment specialist to identify barriers in partnership with that participant and work with researchers to remove the barriers. A third innovative approach uses social media apps to reach participants more directly, which one study has leveraged to increase uptake of medication-assisted treatment among OUD patients.

Some research programs leverage these supplements to catalyze infrastructure development for future studies. For example, the University of Michigan will leverage its Clinical and Translational Science Awards to partner with communities of color, incorporate input from underrepresented and diverse groups into studies, recruit more representative populations, and effectively share study findings.


Future HEAL supplements may recruit researchers from Historically Black Colleges and Universities (HBCUs) and Tribal Colleges and Universities, even though current supplements for supporting diversity and inclusivity among study participants have been made available only to current HEAL-funded investigators.

Pain Therapeutics Development Program

Charles Cywin, PhD, NINDS

The HEAL Pain Therapeutics Development Program (PTDP) supports the identification and development of new analgesics for treating acute or chronic pain by providing resources that most academic and small businesses lack, such as infrastructure to translate basic research findings into drug candidates, expertise in the drug discovery and development disciplines required for success, experience with navigating regulatory pathways to the clinic, and experience in obtaining outside funding (e.g., from venture, biotech, and pharma).  PTDP supports multiple stages of development, such as planning, screening, mechanism and model work, and biomarker development. It specializes in the optimization stage, which is designed to result in a Phase II-ready asset for handoff to the Early Phase Pain Investigation Clinical Network (EPPIC-NET) or licensing.  A unique aspect of PTDP is the formation of a lead development team, with the grantee serving as chair. This team is augmented by consultants with pharmaceutical industry experience as well as NIH staff from any of nine participating ICs. Furthermore, PTDP provides access to a suite of contracts to fill any knowledge or skill gaps in a grantee’s team.   

All PTDP projects begin with a preparatory UG3 phase that has two goals: (1) identify and conduct the studies necessary to meet the criteria to progress to the Lead Optimization Stage, and (2) design execution plans and Go/No-Go milestones for the subsequent UH3 award. Progression to the UH3 award is conditional upon administrative review of milestone achievement and portfolio considerations, which allows for de-risking of projects and advancement of only projects with the most promise. Four of the six projects funded when PTDP began in 2019 underwent UG3/UH3 transition in 2021. PTDP plans to launch up to 17 projects between 2021 and 2025; 3 projects have launched so far in FY21.

Integrative Management of Chronic Pain and OUD for Whole Recovery Network

Shelley Su, PhD, National Institute on Drug Abuse (NIDA)

Although 40 to 60 percent of people with OUD also have CP, few evidence-based interventions exist to support these patients. Notably, both ethnic and racial minorities as well as women frequently experience inadequate pain management, and fatal overdoses are disproportionately common among racial and ethnic minorities.

The Integrative Management of Chronic Pain and OUD for Whole Recovery (IMPOWR) Network aims to generate evidence-based, patient-centered solutions for integrated management of co-occurring CP and OUD, and to rapidly disseminate knowledge to stakeholders to improve population health. Thus, IMPOWR set five goals:

  1. Invest in a wide range of sustainable approaches to CP and OUD management by serving diverse communities in different health care settings throughout the United States
  2. Embrace a whole-patient approach, recognizing in particular the likelihood of co-occurring psychiatric disorders and persistent stigma, which may necessitate broader inclusion criteria
  3. Be mindful of the health disparities and health system inequities that threaten access to life-saving treatments, particularly for women, African Americans, and Latinx people
  4. Maximize the potential for incorporation of evidence-based interventions into standard practice via stakeholder engagement
  5. Expand the next generation of diverse clinicians and research scientists at the intersection of OUD and CP by encouraging co-leadership on primary studies and mentorship on pilot projects

IMPOWR funds four research centers, which run nine unique clinical trials that together represent a $50 million dollar investment over 5 years. These trials are grouped into three thematic buckets (i.e., care delivery models, behavioral treatment approaches for pain management, and buprenorphine dosing strategies). Four of these clinical trials target OUD treatment initiation, and five trials emphasize retention in treatment. All of the funded trials emphasize implementation science to maximize the likelihood that evidence-based interventions will be incorporated into standard practice. In addition, each project is committed to including underserved populations and supporting the next generation of scientists. IMPOWR also funds an associated Coordination and Dissemination Center that generates resources for research, including a single composite screening instrument for CP and OUD, as well as various educational materials tailored to a wide range of audiences. IMPOWR engages patients, private, and public partners early and frequently so that outcomes relevant to each stakeholder population are captured, treatment adherence is more likely, and private and public partners can change clinical, funding, and policy practices according to evidence.  


Applicants for IMPOWR funding have proposed pain management interventions that pursue behavioral, pharmacological, and health system-centered approaches. The primary challenge to implementing patient-centered approaches into standard practice, especially behavioral treatments, is convincing health systems and payors of their worth.

To date, no IMPOWR studies have launched peer support programs. However, some IMPOWR research centers have considered pilot studies for peer support or peer navigation of pain management, which would be developed along with people with lived experience who serve on a stakeholder board. Stakeholder guidance is critical for any study with a peer support component.

Highlighted New HEAL Released Funding Opportunity Announcements for 2022 Awards

Optimizing Therapies for Sickle Cell Disease Pain Management

Wen Chen, PhD, NCCIH

Pain is the most common complication of sickle cell disease (SCD), including severe acute pain crises, chronic persistent pain, and neuropathic pain. Existing treatments often fail to address comorbidities (e.g., anxiety, stress, sleep disturbances) that may worsen pain. Pain is further exacerbated by disparities in receiving quality comprehensive care among patient populations composed primarily of racial and ethnic minorities. These disparities are attributed to factors such as racism, delayed growth and puberty, and opioid use, as well as stigma associated with SCD, which impacts health outcomes, health-seeking behavior, and patient-provider interactions. The biopsychosocial model of pain management should guide efforts to address SCD pain, ideally through reducing stigma and implementing multicomponent or whole-person health approaches with the goal of improving overall health.

Two HEAL Initiative Requests for Applications (RFAs) support pain research in the context of SCD. The first, titled “Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain” (RFA-AT-22-004), funds studies embedded in health care systems (HCSs). Pragmatic trials collect most data as part of clinical care, primarily through electronic health records (EHRs). Implementation studies focus on putting research findings into real-world practice, generally at the system or provider level, though patient-level implementation outcomes can also be studied. All clinical trials funded by this RFA must be conducted through HEAL’s Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Program Coordinating Center. Awardees will also work with the HCS Research Collaboratory Coordinating Center (CCC) to facilitate further planning and refinement of proposed trials in partnerships with HCSs.

The second RFA, titled “Sickle Cell Disease Pain Management Trials Utilizing the Pain Management Effectiveness Research Network Cooperative Agreement” (RFA-AT-22-005), funds effectiveness trials. All funded studies must randomize participants individually, collect in-person measures for research purposes, or deliver an intervention in a standardized fashion. Funded trials will be conducted within the infrastructure of the HEAL Pain Management Effectiveness Research Network (ERN). Awardees will receive clinical, biostatistical, and recruitment support from the National Center for Advancing Translational Sciences (NCATS) Trial Innovation Network (TIN).

Advancing Health Equity in Pain Management and New Concept for Health Equity in Pain and Comorbid Conditions

Cheryse Sankar, PhD, NINDS

Although health disparities in pain care are well-documented, few interventions exist to mitigate or eliminate them. Disparities in pain care likely stem from a combination of factors existing across multiple levels of influence (e.g., individual, interpersonal, communities, systems) over an individual’s lifespan and across the pain care continuum. Racially and ethnically minoritized groups and persons with low socioeconomic status (SES) predominantly experience health disparities; however, NIH identifies several populations as experiencing health disparities, and HEAL’s efforts to advance health equity include all such groups.

The biopsychosocial factors related to disparities in pain are complex, overlapping, and highly variable across populations. Pain reporting is subjective and can be influenced by cultural and individual differences, as well as the physiological consequences of chronic stress that impact pain perception and sensitivity. In addition, pain assessment and decisions about pain treatment can be vulnerable to conscious or unconscious bias at the provider level. Racism and other forms of discrimination also extend beyond the behavior of individuals and are embedded into societal, institutional, organizational, and governmental structures.

The goal of a recent RFA, titled “Advancing Health Equity in Pain Management” (RFA-NS-22-002), is to accelerate development, testing, and implementation of culturally and linguistically appropriate evidence-based interventions to reduce susceptibility to CP, and improve patient outcomes in populations that experience health disparities. Interventions of high priority for this RFA would aim to mitigate or eliminate the effects of bias, stigma, and discrimination in provision of care and treatment decisions; mitigate or eliminate socioeconomic, environmental, and other barriers to quality pain assessment, treatment, and management; or address multiple socioecological domains and levels of influence.

A recently published NOSI, titled “Advancing Health Equity in Pain and Comorbidities” (NOT-NS-22-040), similarly supports the development of novel interventions or adaption of existing interventions to mitigate symptoms and improve health outcomes in underserved populations that suffer disproportionately from pain and prevalent comorbid conditions, such as OUD, mental health disorders, and chronic health conditions. Interventions of high priority for this NOSI are those that are culturally and linguistically tailored to population(s) that experience health disparities, address acute and/or CP with at least one other comorbid condition, or address at least one social determinant of health.


Led by Irma Rodriguez, IPRCC

NINDS is developing methods to effectively disseminate findings from its funded studies, and recently held a workshop on advancing health equity, diversity, and inclusion. In addition, both the recent RFA and NOSI emphasize stakeholder engagement, and investigator-developed engagement strategies will be used as a metric for determining eligibility and priority for grants.

Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management

Wen Chen, PhD, NCCIH

Myofascial tissue is implicated in many pain conditions, including headache and migraine, temporomandibular disorder (TMD), and neck and shoulder pain. Myofascial pain can be effectively managed by nonopioid treatments. However, insurance often does not reimburse for such treatments because research on the mechanisms underlying myofascial pain and its treatment, and knowledge about the interaction of the fascia with other portions of the myofascial unit, are limited.

To address this major knowledge gap, the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and NCCIH co-sponsored a workshop in 2020 titled “Quantitative Evaluation of Myofascial Tissues: Potential Impact for Musculoskeletal Pain Research.” During the workshop, researchers discussed how pain involving myofascial tissue typically occurs in two phases: In the latent stage, focal nodules lead to pain only when pressure is applied, whereas in the active stage, nodules produce spontaneous pain that is exacerbated with palpation. Neither physiological explanations for nor quantitative evaluations of those phases currently exist.

A HEAL RFA titled “Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management” (RFA-AT-22-003) supports research to identify candidate indicators and biomarkers of myofascial pain, with the overall aim to develop cutting-edge technologies for the study of myofascial tissues in the context of pain. The R61 Phase (up to 3 years) includes observational studies and planning for the R33 Phase, during which quantitative measures that differentiate abnormal myofascial tissues in latent and active pain stages from healthy tissues are identified and developed. The R33 Phase includes interventional studies that test biomarkers’ abilities to monitor responses and predict outcomes of existing and putative treatments to relieve myofascial pain (e.g., physical force-based manipulations, thermotherapies, local chemical-based injection therapies). Because these projects require collaboration among a diverse field of investigators, HEAL has sponsored two technical assistance webinars (in December 2021 and January 2022) to support this research.

Clinical Pain Research Workforce Survey

Andrew Siddons, MPH, NINDS, and Laura Wandner, PhD, NINDS

The IPRCC Clinical Pain Research Workforce Survey aimed to identify factors contributing to decisions to pursue and leave pain research careers. IPRCC will use the survey data to inform the broader research community about career development needs and encourage stakeholders to develop resources necessary to strengthen the pain research workforce.

The survey consisted of 29 questions about experiences with research, training, and mentoring; career challenges; changes that could prompt a return to research; and research funding. Approximately 400 respondents completed the survey, half of whom had either left research or were early-career researchers. In general, those who left research had been early in their careers and were less likely to have received formal training, federal funding, or mentorship. Established pain researchers were more likely to have received federal funding, regardless of whether they eventually left research.

Former researchers were less interested in incentives to return to research if they left early in their careers compared to those who had been more established. Early-career investigators emphasized a need for support and funding from their institutions, as well as protected time to perform research. Established investigators were more likely than early-stage investigators to report that NIH support would influence a decision to remain in or return to research.


The IPRCC highlighted two opportunities to support the pain research workforce:

  • Emphasize K-series grant mechanisms, which can provide career development support and mentorship to boost retention of junior and mid-career investigators in pain research.
  • Partner with pain research organizations (e.g., Association of University Anesthesiologists) to distribute similar surveys and explore opportunities to improve and expand the pain research workforce

HHS Overdose Prevention Strategy

Rebecca Baker, PhD

The Department of Health and Human Services’ (HHS’s) overdose prevention strategy focuses on equity, collaboration, and stigma reduction and includes four key goals, all of which can be addressed by HEAL:

  1. Primary prevention, including conducting clinical research in pain and pain management, working with youth and high-risk populations, addressing social determinants of health, advancing equity in pain management, and preventing overdose
  2. Recovery support (newly added by the Biden administration), including enhancing research on relapses, recognizing that addiction is a lifelong disease, and providing support throughout the lifespan
  3. Evidence-based treatment, requiring support for research by NIH and HEAL partners
  4. Harm reduction (also newly added by the Biden administration), including naloxone availability and delivery, fentanyl test strip availability, and rapid-response data collection

The HHS strategy also includes cross-cutting research themes that align with HEAL Initiative efforts. These themes emphasis engaging patients and other stakeholders in research, increasing diversity and inclusion among researchers and study participants, finding solutions to stigma, and harnessing the power of data.

New HEAL Pain Research Concepts 2022

Research Adoption Partnership

Rebecca Baker, PhD

The President’s FY22 budget proposed an extra $270 million for HEAL research. If awarded, the following new research ideas have been proposed: Coordinated Approach to Pain Management, Rapid Response Data Driven Research, Basic and Translational Neuroscience in Pain and Opioid Misuse, and Research Adoption Partnership.

In addition, the increased budget would enable expansion of approved concept areas:  summarized below: Research to Address Polysubstance Use, Social Determinants of Health, Medication Development for Opioid and Stimulant Use Disorders, Advancing Health Equity through HEAL Research, and Harnessing the Power of Innovation to Treat Pain.

A proposed Research Adoption concept would improve rapid, streamlined dissemination of evidence-based interventions and strategies, which is particularly relevant to IPRCC given its focus on moving pain interventions through the research pipeline. Proof-of-concept projects emphasize locally driven goal setting and action planning based on pain research findings. This concept would be highly connected to data efforts (e.g., Actionable Data to Inform Research-Driven Decisions, or Data2Action) to provide relevant data infrastructure support and promote sustainability of new practices. A National Research Coordination Center would provide further support for the broader dissemination of these local proof-of-concept projects on a national scale.


Led by Robert Kerns, PhD, IPRCC

The IPRCC discussed research and treatment gaps at the intersection of pain and OUD, emphasizing the importance of adapting research and intervention strategies based on community engagement and feedback:

  • For some populations, recovery from CP or OUD alone may be insufficient without a complementary focus on reintegration; for example, veterans with CP or OUD want to feel healthy and “normal” rather than simply free of OUD or CP.
  • Pain research has not sufficiently included individuals who live with CP and become reliant on opioids but eventually lose access to treatment and turn to illicit substances, which can lead to overdose or suicide. Such gaps in community engagement with research must be considered when addressing major public health problems.
  • To test the hypothesis that affiliation with faith-based communities is protective against addition, studies should consider recruiting from faith groups.
  • OUD is often driven by mental health, prior trauma, abuse, neglect, or struggle with personal sexual identity. The National Institute for Mental Health (NIMH) has therefore encouraged collaborative care models and integration of mental health services into settings that screen and treat OUD, including primary care.
  • HCPC should engage with people in recovery to gain valuable perspective on the needs of people with OUD and viable harm reduction strategies.

Coordinated Approaches to Pain Management in Health Care Systems

Linda Porter, PhD, Director, Office of Pain Policy, NINDS

The Coordinated Approaches to Pain Care in HCSs concept aims to bring effective and evidence-based models of coordinated pain care into HCSs with an emphasis on populations with the greatest need. Pain care is often delivered as a single modality in one setting, which leads to inadequate pain management. Coordinated, personalized care should include medication management, procedures, physical and psychological therapies, patient self-management strategies, and complementary approaches as appropriate to manage pain. The care plan should be centered on patient goals and leverage existing HCS resources delivered though a coordinated approach and supported by payor policies and guidelines. This concept adopts a variety of coordinated approaches to pain management, as follows:

  • Use implementation science to embed existing evidence-based coordinated pain care models into public and private health care settings
  • Leverage comparative effectiveness studies of innovative coordinated care models with implementation science methodology to embed effective approaches into HCSs
  • Include multidisciplinary care providers (including primary care) and implementation scientists on study teams
  • Include patients, payors, and policy makers among stakeholders to ensure that the study and outcomes are appropriate to the study population, and that outcomes are meaningful and realistic
  • Coordinate and integrate studies using a coordinating center to ensure that findings are durable and applicable to a broad spectrum of settings

Outcomes of this research concept should include HCS-embedded evidence-based coordinated pain care based on the biopsychosocial model of pain and combined multidisciplinary evidence-based pain treatments, which may be centered in specialty services or primary care (with integrated referral to specialty services).


Led by Daniel Carr, MD, IPRCC; Kathy Hammitt, IPRCC

The IPRCC discussed potential elements to incorporate in studies associated with this concept based on past successes:

  • Screeners have been successfully used in transitional pain services to determine which patients are at risk of poor pain medication management and outcomes.
  • Incorporation of Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) provides a potential financial benefit to HCSs.
  • Care coordinators can facilitate long-term adherence to a management plan, particularly when multiple specialties are involved; provide the patient with education; assist the patient with access, time, and cost assessment; and assist with resource location.

Re-Alignment of the HEAL Biomarker Program: Translational Tools to Facilitate Clinical Trials for Pain Therapeutics

Mary Ann Pelleymounter, PhD, NINDS

Biomarkers are used for both therapeutic development and treatment decisions in clinical practice. A wide variety of biomarkers exist, including disease trajectory, target engagement, therapeutic response prediction, diagnostic, pharmacodynamic, and prognostic biomarkers, all of which are defined in the Biomarkers, Endpoints, and Other Tools (BeST) Glossary.  

Past Funding Opportunity Announcements (FOAs) focused on pain biomarker development and validation include “Discovery of Biomarkers, Biomarker Signatures or Endpoints for Pain” (RFA-NS-18-041) and “Analytical and/or Clinical Validation of a Candidate Biomarker for Pain” (RFA-NS-18-046). These FOAs funded nine projects; however, no applications included biomarkers for predicting or monitoring therapeutic response, and no meritorious applications focused on validation-stage biomarker development. To address these portfolio gaps, HEAL solicited research on biomarkers for therapeutic mechanism-specific response monitoring, response prediction, and patient stratification. In addition, HEAL emphasized the need for biomarker signature development across multiple pain conditions, collaborations across pain types and groups, and mechanistic pain research.

The re-aligned pain biomarker proposal, titled “Translational Tools to Facilitate Clinical Trials for Pain Therapeutics” (RFA-NS-21-015), supports the development of validated response monitoring and prediction pain biosignatures that facilitate Phase II clinical trials for pain therapeutics through a staged but flexible program. This FOA encourages collaborative and team-based research that should produce a biomarker signature that monitors treatment response in at least one pain disorder, stratifies patients by predicted treatment response, and can be used in Master Protocol clinical designs. These biomarkers should also be useful for Investigational New Drug (IND) packages and should meet the requirements for FDA’s Biomarker Qualification Program.


Led by David Williams, PhD, IPRCC

Biomarkers are valuable alternatives to subjective self-reports of pain, and they are essential when a patient cannot self-report (e.g., infants, people who cannot communicate because of cognitive impairment, animals). However, patients often fear clinicians’ responses when self-reports and biomarker readouts conflict. Although biomarkers will primarily be used to monitor responses to treatment rather than as a substitute for pain reports, validation of biomarkers will nonetheless require alignment with patient experiences.

Joint Pain and Innervation Research

Leslie K. Derr, PhD, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Joints consist of multiple tissues and structures, all of which are involved in arthritis. Molecules released following damage to these tissues can directly activate pain-mediating neurites from the dorsal root ganglion (DRG). Furthermore, tissue degeneration induces growth of these neurites across joint tissues, which may increase pain. These recent findings suggest that better understanding of how damage-associated molecules from different joint tissues activate pain neurons could lead to novel approaches to treat pain. A recent Request for Information (RFI), “Joint and Pain Innervation Research” (NOT-AR-22-008), addresses this opportunity by soliciting  information about the state of the science with respect to the following:

  • Determining the location of afferent neurites of specific types of DRG sensory neurons
  • Studying changes in joint neurites with age, sex, activity, and other factors
  • Mapping in-growth of neurites of specific types accompanying degenerative changes and pain
  • Understanding joint-specific and shared patterns of changes in innervation with age or disease
  • Validating animal model maps in human tissue

The ultimate goal of the RFI is to develop new treatments for joint pain by identifying new pain inhibitors and strategies that prevent progression of joint pathology and dysfunction.


Led by Christine Goertz, DC, PhD, IPRCC; Sue Pinkham, IPRCC

Clinical research is hindered by a lack of mechanistic knowledge regarding how neurites change with activity, age, and disease progression, especially within and across joints. Only after basic mechanisms are determined can researchers effectively address patient experiences and quality of life. Mechanistic insight can be further gained through research into the following:

  • Interactions of complementary and integrative health approaches with neurites and joint components.
  • Influence of rare diseases (e.g., Ehlers-Danlos Syndrome) on joint components and compartments.
  • Mapping of sensory neurons.
  • Involvement of neurotransmitters in joint pain.

Pain Research Workforce Enhancement

Laura D. Wandner, PhD, NINDS; DP Mohapatra, PhD, NINDS

Pain research faces an urgent need to establish best practices in clinical pain management, especially for nonopioid mechanisms. The ability to meet this need is hampered by a limited workforce pipeline for pain researchers. Efforts to improve the pipeline would benefit from cross-institutional mentoring and increased collaboration on grant applications among basic, translational, and clinical pain researchers.

The HEAL MDWG and NINDS Council have approved three pain management workforce concepts, summarized below:

  1. Ensure that a diverse pool of highly trained scientists is available to expand and enhance the clinical pain management workforce by developing a national program (modeled after the National Child Neurology and Neurosurgery K12s) to provide quality mentorship for early-stage clinical pain researchers.
  2. Establish a national pain management coordinating center where early-stage pain researchers funded by different ICs are connected with experienced researchers to promote mentorship, collaboration, and communication across the continuum of pain research.
  3. Implement an advanced Postdoctoral-to-Independent Career Transition Award to expand and diversify the pool of independent investigators for pain and substance use disorder (SUD) research. This award would support advanced postdoctoral researchers in basic, translational, and clinical pain research under theK99/R00 mechanism with a timely transition to independent, tenure-track, or equivalent faculty positions. Supported researchers would also be encouraged to pursue networking and collaboration opportunities through the national pain management coordinating center.


Led by Beth Darnall, PhD, IPRCC

The Coordinating Center concept would support all K and T series awardees. The Coordinating Center would welcome participation from researchers at all career stages funded by NIH, and could specifically encourage trainees in translational research to participate, which would support both pain- and addiction-related research priorities for the HEAL Initiative.

Institute and Center New Pain Research Concepts for Awards in 2022

Transformative, Collaborative, Interdisciplinary Research in Chronic Pain

Gayle Lester, PhD, NIAMS

NIAMS issued a NOSI (“Promoting Pain Research Within the NIAMS Mission Areas” [NOT-AR-22-007]) to notify the research community of its interest in receiving applications focused on mechanisms of CP in inflammatory, degenerative, and rare genetic diseases in adults and children for disease areas within the NIAMS mission (e.g., rheumatic, osteoarthritis, bone, muscle, skin). The NOSI would support transformative basic, clinical, and translational projects that integrate precision medicine approaches to address significant challenges in prevention, treatment, and health equity in CP, which may require highly collaborative research infrastructure. Supported projects are expected to generate high-impact research resources and foster discovery-based, paradigm-shifting, or hypothesis-generating science.

NINDS FY22 Pain Concepts

Michael Oschinksy, PhD, NINDS

NINDS supports four primary categories of pain research and has approved several research concepts for new funding opportunities in 2022, as follows:

  • Basic Science, Mechanisms, and Discovery: NINDS will increase the pay line for pain applications (mostly R01 basic science applications) for paradigm-shifting, team-based research projects on the neurobiology of pain in both human and animal subjects, the role of the gut microbiome in chronic neuropathic pain, and the pathophysiology of migraine and headache.
  • Tool Development for Pain Research: NINDS will support research involving medium and large animal models (e.g., for joint pain), translational tools to facilitate clinical trials for pain therapeutics (e.g., biomarker signatures), resource grants for pain-technology for dissemination and integration, and bioengineering resource grants to accurately assess pain and pain circuits.
  • Research Training for Pain Research: NINDS will fund fellowships and career development/transition awards, as well as awards for training clinician researchers, with an emphasis on increasing diversity in the biomedical pain research workforce.
  • Basic Science and Clinical Pain Research in Humans: NINDS will support research on clinical pain phenotyping and outcome measure assessment, translational neural devices to treat pain, and headaches in pediatrics.

Expansion of NIH-DOD-VA Pain Management Collaboratory Research Activities

Peter Murray, PhD, NCCIH

The goal of the NIH-DOD-VA Pain Management Collaboratory (PMC) is to test implementation and evaluation of nonpharmacologic approaches for the management of pain and common co-occurring conditions in the military and veterans’ health care systems. Since its establishment in 2017, the PMC has funded 11 large-scale, multisite, pragmatic clinical trials as well as the Pain Management Collaboratory Coordinating Center (PMC3) to support these trials. The PMC3 has tasked working groups to focus on different trial-related domains, including EHRs, stakeholder engagement, phenotypes and outcomes, ethical and regulatory policies, study design and biostatistics, data sharing, and implementation science.

The new PMC program would expand the scope of pain conditions studied beyond musculoskeletal pain to include post-concussive pain, headache, burn pain, and postsurgical pain. Supporting pragmatic effectiveness trials for nonpharmacologic pain interventions would remain central, but this round of research would include a particular focus on interventions with little effectiveness data. The new program also acknowledges the potential for multicomponent interventions to simultaneously address pain and common co-occurring conditions (e.g., post-traumatic stress disorder, suicide ideation, anxiety). Additional priorities for the new program include implementation science trials and evaluation of coordinated care programs for pain management in service members and veterans.

IC Pain Research Concepts

Linda Porter, PhD, Director, Office of Pain Policy, NINDS

The IPRCC reviewed the following updates from additional ICs that will fund pain research in 2022:

  • The National Institute of Dental and Craniofacial Research (NIDCR) is discussing a coordinated and interdisciplinary approach to advance the science of TMD to address the persistent challenge of diagnosis and management. NIDCR may partner with other ICs (e.g., NIAMS, National Institute on Aging [NIA], NINDS, NIBIB, NIMH) to study multiple facets of TMD, including joint-specific conditions, myofascial and nervous system involvement, gender imbalance, surgical complications, and its status as a chronic overlapping condition.
  • NIA will receive funding but has yet to propose specific research concepts.
  • The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has proposed a research concept (Advancing Research on Mechanisms and Management of Pain for Diseases and Conditions) that is designed to solicit broad basic, translational, and clinical research studies and efforts to develop new measures, tools, and methods to inform understanding of pain mechanism and pain management for conditions within NIDDK’s mission (e.g., intestinal disorders, diabetic neuropathic pain).

Additional Research Concepts

The IPRCC discussed additional research gaps that should be considered for future funding:

  • Patient-centered opioid tapering, with attention to the heterogeneity of CP and the patient population
  • Appropriateness of opioid treatment based on individual patient risks
  • Fibromyalgia
  • Dysautonomia
  • The intersection of SUD and pain, including use of cannabinoids and cannabis
  • Data harmonization and deep phenotyping, which can be supported by IMPOWR and HEAL-funded coordinating centers

The IPRCC also acknowledged that HEAL’s funding opportunities often require investigators to develop new expertise. This prescription is unlikely to change because, unlike NIH, HEAL FOAs are generally directed by Congress.

Approval of Previous Minutes and Adjourn

IPRCC members voted to approve the minutes from the IPRCC’s previous meeting.

Pursuant to guidelines in the Affordable Care Act, IPRCC publishes science advances related to pain research. IPRCC will solicit advances from its members for publication after this meeting.

Finally, Dr. Helmick will be retiring from the federal government and concluded his final IPRCC meeting by encouraging the IPRCC to pursue pain research from a public health perspective.

The meeting was adjourned.

We certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.

Linda Porter, PhD
Designated Federal Official
Interagency Pain Research Coordinating Committee
Director, Office of Pain Policy, National Institute of Neurological Disorders and Stroke
Walter Koroshetz, PhD
Chair Interagency Pain Research Coordinating Committee
Director, National Institute of Neurological Disorders and Stroke
These minutes have been formally approved by the committee.


This meeting summary was prepared by Rose Li and Associates, Inc., under contract to the National Institute for Neurological Disorders and Stroke (NINDS). The views expressed in this document reflect both individual and collective opinions of the meeting participants and not necessarily those of NINDS. Review of earlier versions of this meeting summary by the following individuals is gratefully acknowledged: Christina Tricou, Caroline Sferrazza, Nancy Tuvesson.

IPRCC Agenda, November 22, 2021 

10:am ET to 3:30 PM ET


Welcome and Introductions  

Meeting Cochairs: Dr. Walter Koroshetz, Director NINDS, Chair IPRCC and Dr.  Helene Langevin, Director NCCIH

Introduce Ad Hoc Members 

Announce Retirement  


What if?  2022 Pending NIH Budget for Pain Research: HEAL and trans-NIH Allocations

 Dr. Walter Koroshetz, NINDS   


Highlighted New HEAL Programs Awarded in 2021

HEAL Community Partnership Committee
Dr. Linda Porter, NINDS

Diversity and Patient Engagement Supplements
Dr. Cheryse Sankar, NINDS 

HEAL Pain Therapeutics Development Program
Dr. Charles Cywin, NINDS 

Dr. Shelley Su, NIDA 


Highlighted New HEAL Released FOAs for 2022 Awards

Sickle Cell Disease Pain Management Trials

Advancing Health Equities in Pain Management and New Concept for Health Equities in Pain and Comorbid Conditions
Dr. Cheryse Sankar, NINDS with Discussion Lead Irma Rodriquez, IPRCC 

 Myofascial Pain Biomarkers
Dr. Wen Chen, NCCIH 

11:55am  BREAK

Clinical Pain Research Workforce Survey Update

 Andrew Siddons and Dr. Laura Wandner, NINDS


HHS Overdose Prevention Strategy Rebecca Baker


 New HEAL Pain Research Concepts 2022

Research Adoption Partnership
Dr. Rebecca Baker with discussion lead IPRCC 

Coordinated Approaches to Pain Management in Health Care Systems
Dr. Linda Porter with discussion leads Daniel Carr and Kathy Hammitt, IPRCC 

Translational Tools for Pain Therapeutics: Biomarkers
Dr.  Mary Ann Pelleymounter with discussion lead David Williams IPRCC  

Innervation and Joint Pain
Dr. Leslie Derr, NIAMS with Discussion Leads Christine Goertz and IPRCC 

Pain Research Workforce Enhancement
Laura Wandner and DP Mohapatra NINDS with discussion lead IPRCC 


Institute and Center New Pain Research Concepts for Awards in 2022

Transformative, Collaborative, Interdisciplinary Research in Chronic Pain

Dr. Gayle Lester NIAMS 


Pain Management Collaboratory expansion

Dr. Peter Murray, NCCIH


Linda Porter, OPPP 

3:30pm  ADJOURN


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