New Opportunities for Advancing Pain Science

Director’s Page
Helene M. Langevin, M.D.

December 30, 2021

This message is jointly authored by NINDS Director Walter J. Koroshetz, NCCIH Director Helene M. Langevin, NIA Director Richard Hodes, NIAMS Director Lindsey A. Criswell, NIDCR Director Rena D'Souza, NIDDK Director Griffin P. Rodgers, and NIH HEAL Initiative Director Rebecca Baker.

From the Hippocratic corpus, the author writes, “I consider the responsibility of medicine to be to entirely relieve the suffering of the sick and to blunt the extremities of disease” (The Art 3.4-7)¹. Note that despite the acknowledgement that disease may only be blunted, in promoting health it is our duty to relieve suffering wherever possible. There has been some success in relieving the suffering due to acute pain, i.e., via local and general anesthesia, non-steroidal anti-inflammatories, and opioids, but we have largely failed in effectively removing suffering due to chronic pain conditions. We need new, nonaddictive acute and more effective chronic pain treatments, and we are approaching a unique opportunity for funding new directions for pain research.

In pursuit of its mission, the National Institutes of Health (NIH) is committed to seek fundamental knowledge about the nature of pain and the application of that knowledge to enhance health and reduce disability. Recognizing the urgent need to improve the management of pain, the Fiscal Year 2022 budget proposals from the President, House, and Senate each provide increased funding for pain research to several NIH Institutes and Centers. This is in addition to increased funding to the Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®, with its integrated goal to reduce opioid use disorder and more effectively treat pain conditions while limiting the risk of addiction.

The NIH Institutes and Centers proposed to receive increases for pain research in Fiscal Year 2022 include: the National Institute on Aging (NIA); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Complementary and Integrative Health (NCCIH); National Institute of Dental and Craniofacial Research (NIDCR); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and National Institute of Neurological Disorders and Stroke (NINDS). Our Institutes have been diligently working to identify priority areas of scientific need within each of our missions and recently issued a Notice of Information alerting potential applicants to current funding opportunity announcements (FOAs) or notices of scientific interest (NOSIs). However, as of this writing, the NIH is still operating under a Continuing Resolution, i.e., guided by legislative mandates that were in effect in Fiscal Year 2021, until a final budget for Fiscal Year 2022 is approved by Congress.

With this message, our Institutes and Centers wish to inform the scientific community of the pain research opportunities that may present themselves if funds become available. The timing is unfortunately very tight—applications may still need to be submitted by the usual application deadlines in January or February 2022 so they can undergo peer review and then be approved by the September 2022 Advisory Council to receive funds in this current fiscal year. Though there is still some uncertainty about the final availability of funds, we are excited by the potential to accelerate discovery and therapy development in this critical area, and we strongly encourage investigators to consider submitting applications that can advance our knowledge of the nature of pain and its treatment. The areas of scientific need identified by the Institutes and Centers are described below:

NCCIH: NCCIH recently issued a NOSI for special pain research topics within its mission to accompany multiple funding mechanisms, such as R01, R21, R34, and R15 grants, as well as an administrative supplement NOSI:

NOT-AT-22-007 “Notice of Special Interest: NCCIH High Priority Pain Research”

This NOSI focuses on a range of pain topics including:

Basic/mechanistic, translational, or clinical research on pain related to sickle cell disease
Basic and mechanistic understanding of myofascial pain
Fundamental science of biophysical force-based interventions to prevent or manage chronic pain
Identifying novel therapeutic targets of pain for non-addictive natural products
The science of music therapies to enhance pain management
Multicomponent pain management intervention development
Trials of complementary and integrative interventions delivered remotely or via mHealth

NCCIH is also considering issuing additional clinical request for applications (RFAs), such as for the NIH-DOD-VA Pain Management Collaboratory.

NIA: NIA recently published the following two Notices of Special Interest (NOSI) highlighting research related to pain, pain management, and opioids that fall within NIA’s mission:

NOT-AG-22-004 “Notice of Special Interest: Research on Pain, Pain Management, and Opioids in Aging”
NOT-AG-22-005 “Notice of Special Interest (NOSI): Availability of Administrative Supplements for Research on Pain, Pain Management, and Opioids in Aging”

Research topics may include, but are not limited to, studies on mechanisms, assessment, treatment, and outcomes of pain and pain-related conditions in aging humans and animal models. NIA welcomes basic and translational research and research training applications that fall within NIA’s mission to support genetic, biological, clinical, behavioral, social, and economic research on aging. Grant types for NOT-AG-22-004 include research, career development, and small business awards, submitted as new and renewing applications, resubmissions, and competing revisions; or administrative supplements for NOT-AG-22-005.

NIAMS: NIAMS has published a Notice of Special Interest (NOSI): Promoting Pain Research Within the NIAMS Mission Areas (NOT-AR-22-007). NIAMS intends to publish a Notice of Special Interest for administrative supplements to add or expand pain-related research under existing NIAMS awards including Institutional Training Awards (T32) and Centers (P30 and P50). A Notice of Intent to Publish will be released for future (2023) funding opportunity announcements designed to advance the understanding of mechanisms of chronic pain in inflammatory, degenerative and rare genetic diseases in adults and children relevant to disease areas within the NIAMS mission. The future FOAs could support transformative basic, clinical, and translational projects that incorporate precision medicine approaches to also address challenges in prevention, treatment, and health equity in chronic pain. It is expected that the research resources generated by the projects will be shared with the community to foster additional hypothesis-generating science related to pain in musculoskeletal and rheumatic diseases.

NIDCR: NIDCR intends to expand pain research within our mission areas in new directions, including:

Temporomandibular joint disorders – Improving Patient-Centered Translational Research (TMD-IMPACT) - This direction will foster basic and clinical research, research training, and translation to evidence-based treatments and improved clinical care.
Role of Dentistry in the Prevention of Opioid Drug Misuse and Abuse – This avenue will support research to establish effective interventions or programs to manage, reduce, or prevent opioid drug misuse and align the opioid prescribing practices of dental professionals with scientific evidence.

In addition, NIDCR plans on publishing a Notice of Special Interest (NOSI) for Administrative Supplements to Support Pain-Focused High Priority Research Areas, such as biomarker signatures or neuroimmune interactions in painful temporomandibular disorders (TMDs); screening for orofacial pain conditions or opioid use disorders (OUDs) in dental settings; enhancing pain assessment; and identifying biological, environmental, or social determinants of disparities in pain perception or management.

NIDDK: NIDDK has published a Notice of Intent to Publish (NOT-DK-22-007) to inform the community of an impending Funding Opportunity Announcement for investigator-initiated research projects proposing novel basic, translational, and clinical studies and efforts to develop new approaches to assess and treat pain for disorders within the NIDDK’s Mission, including diabetic neuropathy; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases. Investigations are expected to provide important new insights into the pathophysiology and clinical features of pain and foster new and improved treatment and pain management strategies for patients.

NINDS: NINDS recently published the following three Notices of Scientific Interest (NOSIs) for pain research that falls within our mission to accompany multiple funding mechanisms including R grants, K grants, U grants that cover basic discovery science of pain mechanisms, tool development to advance pain research, training, basic/clinical research in humans as well as competing revisions to existing NIH grants and contracts:

NOT-NS-22-050 “Notice of Special Interest (NOSI) in NINDS mission relevant Pain Research”
NOT-NS-22-051 “Notice of Special Interest (NOSI) in Migraine and Headache Research”
NOT-NS-22-053 “Notice of Special Interest (NOSI): Pain-Focused Administrative Supplements for NINDS Grants that are Not Focused on Pain Research”

Topics of interest include but are not limited to:

Research on Mechanisms of Pain
Team-based Integrated Clinical and Basic Research on Neurobiology of Pain
Role of the gut microbiome in chronic neuropathic pain
Neurobiology of Migraine and Headache and Headache in Children
Pain Research that can only be approached in Medium and Large Animal Models
Translational Tools to Facilitate Clinical Trials for Pain Therapeutics
Biomarker signatures of pain conditions
Resource Grants for Pain-Technology Integration and Dissemination
Bioengineering Research Grants to develop Technologies to investigate pain and pain circuits
Clinical Pain Phenotyping and Outcome Measure Assessment
Development of Translational Neural Devices to Treat Pain
Fellowships and Career development/transition awards
Awards for the Training of Clinician Researchers in Pain

HEAL Initiative: By the end of 2021, HEAL funded over $2 billion in research in pain and addiction, representing more than 600 research projects across the United States. Advancing research on pain management is a core goal of the initiative. Select funding opportunities are listed below, and new concepts poised for future development are in progress:

¹Scullin SE., Hippocratic Pain. (2012) University of Pennsylvania Scholarly commons.

Helene M. Langevin, M.D.