HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Advance the Study of Chronic Overlapping Pain Conditions (COPCs)
Notice Number:

Key Dates

Release Date:

August 25, 2021

First Available Due Date:
November 05, 2021
Expiration Date:
November 06, 2021

Related Announcements

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

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 Allergy and Infectious Diseases (NIAID)

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 Institute on Drug Abuse (NIDA)

National Institute of Nursing Research (NINR)

National Center for Complementary and Integrative Health (NCCIH)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research (OBSSR)


The purpose of this request for administrative supplements to current NIH-funded studies is to encourage clinical and translational research that will increase our understanding of the prevalence, psychological variables, and response to therapy in those individuals with multiple chronic overlapping pain conditions (COPCs). Recent clinical findings suggest that substantial overlap may exist between chronic pain conditions. Individuals diagnosed with one pain disorder often exhibit characteristics of additional chronic painful conditions or transition to other diagnostic categories. A better understanding is needed of the characteristics of overlapping pain conditions, the progression of these conditions, and therapeutic approaches best suited for treating individuals with COPCs.

Research efforts in chronic pain conditions have focused on single disorders or types of pain such as neuropathic and inflammatory pain. These research efforts have generated a substantial body of information advancing our understanding of the underlying mechanisms of pain onset and development, the transition from acute to chronic pain, and therapeutic targets for treating acute and chronic pain. Over the past twenty years reports have documented the presence of more than one chronic pain condition in subjects with pain. Studies have identified overlap between a number of chronic pain conditions, including lower back pain, fibromyalgia (FM), vulvodynia, endometriosis, functional gastrointestinal disorders such as irritable bowel syndrome (IBS), temporomandibular joint disorder (TMD), migraine, tension headache, low back pain, and urologic chronic pelvic pain syndromes (UCPPS). These results suggest that chronic pain conditions may not be localized conditions but may share symptoms and mechanisms that involve a general central nervous system dysfunction as well as disorder-specific symptoms. More recent evidence is supportive of the idea that chronic pain conditions are complex disorders consistent with a biopsychosocial model of pain and exhibit substantial overlap. Therefore, this is an opportune time to support additional studies that focus on subjects with COPCs who are enrolled in ongoing studies.


A well-established predictor of onset of COPCs is the presence of a chronic pain condition that is characterized by a state of pain amplification. Several studies found that a large percentage of individuals with diagnosed COPCs demonstrate a state of pain amplification and enhanced pain sensitivity. Whether pain amplification represents a risk determinant versus a consequence of COPCs remains to be determined.

Despite our ability to assess multiple facets relevant to COPCs, treatment of COPCs more generally remains challenging. Current interventions retain a focus on sensory aspects of pain despite the knowledge that chronic pain is heavily influenced by biopsychosocial factors. Evidence-based approaches suggest that combinations of traditional and centrally acting medication produce modest benefits for many COPCs and that combining medications with nonpharmacological interventions can produce greater benefits in pain relief and functional status for many of those with COPCs. For example, psychological interventions show significant benefits in individuals with FM, chronic low back pain, and headache. However, clinical pain reductions with these interventions may help only a subset, and overall benefits may be modest at best. Additional nonmedical interventions, such as exercise, also can benefit individuals with COPCs. Despite some positive evidence for combination therapy for COPCs, additional research is needed.

A workshop sponsored by the NIH Pain Consortium was held in 2012 titled "A Workshop on Chronic Overlapping Pain Conditions". It brought together researchers with expertise in various pain conditions and other relevant expertise to discuss these conditions and to develop a forward-thinking research agenda. The workshop focused on the current understanding of chronic overlapping pain conditions, their etiology, risk factors, mechanisms of disease, outcome measures, and diagnosis. An important outcome of that workshop was the development of a Chronic Overlapping Pain Screener, a research tool to assess shared symptoms and characteristics across COPCs. The recommendations derived from this workshop have, in part, informed the development of this request for administrative supplements.

Research Objectives

Substantial NIHfunding, particularly within the Helping to End Addiction Long-term (HEAL) Initiative, has been allocated to establish and follow different cohorts of patients with chronic pain. The administrative supplement mechanism will allow NIH to leverage existing studies to examine and follow subsets of enrolled participants with COPCs. The additional funding will cover cost increases that are associated with achieving certain new research objectives, such as additional phenotyping and analyses, as long as the research objectives are within the original scope of the peer reviewed and approved project.

Some of the overlapping pain conditions that could be studied include two or more of: migraine, tension headache, temporomandibular joint disorder, generalized pain conditions, , endometriosis, urologic chronic pelvic pain, vulvodynia, fibromyalgia, chronic low back pain, chronic fatigue syndrome, and functional gastrointestinal disorders such as irritable bowel syndrome. Studies that would be possible to complete with administrative supplements include those providing a better understanding of the epidemiology of chronic overlapping pain conditions, risk factors for COPCs and the response of COPCs to therapeutic interventions. This will be accomplished by enhanced phenotyping of participants already enrolled in HEAL trials and other clinical studies, and additional analyses of the final study datasets.

Specific areas of research that will be considered high priority for this administrative supplement request are:

  • Studies of COPC disease progression and remission within established HEAL cohorts
  • Refining of phenotypes relevant to COPCs
  • Identification of potential therapeutic interventions for COPCs
  • Examinations of functional outcomes, such as changes in sleep and physical activity in subjects with COPCs
  • Collection of longitudinal data to analyze co-modifiers of pain such as depression or depressive symptoms, anxiety and other psychopathological conditions that potentiate pain in COPCs
  • Concomitant or new chronic conditions and their effect on outcomes for those with COPC

Note: Applications that propose an additional clinical trial or any other study designed to test and administer an additional intervention are not appropriate for this administrative supplement.


  • Applicants must have at least 18 months of active support remaining on the parent grant as of the supplement application due date. The supplement period of support cannot exceed that of the parent grant. Grant awards entering a no cost extension within 18 months of the application date are not eligible.
  • The cohort to be studied in the parent award to identify and/or quantify the presence of and/or risk factors for COPCs must be described in the administrative supplement request. This should include an assessment of the feasibility of recruiting participants from the parent cohort who are eligible for the proposed COPC research with supporting data.
  • Methods to collect additional data to study COPCs must be described, including a description of how this data will be collected within the framework of the parent grant activities. The approach should clearly justify the rationale for the selection of the COPC measures or outcomes, and any additional adverse effects associated with COPC data collection. Applicants must propose use the Chronic Overlapping Pain Screening Tool (please see this link for more information) for assessing participant symptoms and characteristics. Applications that do not include use of the COPC Screening Tool will be considered non-responsive to this notice.
  • The plan to analyze COPC measures/outcomes collected as part of the additional supplement activities should be described.
  • Budget requests should reflect costs that are necessary and reasonable to complete the work described in the supplement application. Applicants are expected to have readily available the participant cohort and data system necessary to complete the proposed supplemental work.

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.

  • PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

  • Application Due Date(s) Applications will be accepted through November 5, 2021, by 5:00 PM local time of applicant organization. The NOSI expires on November 6, 2021.
  • For funding consideration, applicants must include NOT-NS-21-068 (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.
  • Requests may be for up to 3 years of support and cannot exceed more than $125,000 in direct costs per year.
  • The total budget for all years of the proposed project must be requested in Budget Period 1. Do not complete Budget Periods 2 or 3. They are not required and will not be accepted with the application. The number of years of support requested for this administrative supplement cannot exceed the remaining number of years for the parent grant.
  • The Research Strategy section of the application is limited to 6 pages
  • Applications non-responsive to the terms of this Notice will be not be considered for this initiative.
  • Review criteria, in addition to those described in PA-20-272, include the following:
    • Does the PI(s)/PD(s) have expertise in pain management and/or addiction appropriate for the study of COPCs?
    • Does the application propose to engage -individuals with chronic pain and/or with OUD, providers, and other relevant stakeholders in identifying key questions regarding COPCs, chronic pain management, or opioid use and treatment?
    • If successful, does the application have the potential to be add significantly to our understanding about the risk factors for and management of COPCs?
  • Administrative supplement applications to PA-20-272 must use the application form package with the Competition ID that contains FORMS-F-ADMINSUPP .
  • Investigators planning to submit an application in response to the NOSI are strongly encouraged to contact the appropriate Institute or Center contact listed in the NOSI to discuss the proposed project in the context of the parent award. Questions specific to this NOSI should be sent to the contact listed in the NOSI.


Please direct all inquiries to:

Linda L. Porter, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Email: porterl@ninds.nih.gov

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices