Funded Projects

NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program: Mechanistic Research Centers (U19 Clinical Trial Optional)
NOFO Number: RFA-AR-19-026
Summary:

The University of Michigan (UM) will lead a Mechanistic Research Center (MRC) as part of the broader BACPAC initiative that will take patients with chronic low back pain (cLBP) and use a patient-centric, SMART design study to follow these individuals longitudinally as they try several different evidence-based therapies while mechanistic studies are overlaid to draw crucial inferences about what treatments will work in what patient endotypes. Interventional Response Phenotyping describes the need in any precision medicine initiative to phenotype participants based on what therapies they do and do not respond to so that one can later link mechanistically distinct disease endophenotypes with those who preferentially respond to therapies targeting those mechanisms.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Support Career Enhancement Related to Clinical Research on Pain (Admin Supp – Clinical Trial Not Allowed)
NOFO Number: NOT-NS-21-048
Summary:

There are numerous pharmacological and non-pharmacological interventions for chronic low back pain, yet no treatment is universally effective. This award supports an early career physician to develop skills to prepare for a career in clinical pain research in an environment aiming to understand patient characteristics that predict differential responses to pain interventions and thus allow for tailored treatments. This research assesses the impact of mindfulness-based stress reduction on pain interference reported by people with chronic low back pain and explores neurobiological effects of mindfulness-based stress reduction through advanced imaging and clinical assessments.

NOFO Title: HEAL Initiative: Advancing Health Equity in Pain and Comorbidities (R61/R33 Clinical Trial Required)
NOFO Number: RFA-NS-22-002
Summary:

Back pain, including low back and neck pain, is one of the most prevalent and disabling pain disorders. Treatment requires ongoing self-management, but most healthcare systems do not support self-care and instead focus on costly, provider-dependent therapies that remain inaccessible to many Black and Hispanic Americans and individuals with less education and income. This project will address these health disparities by developing a personalized self-management treatment program that includes pain education, mindfulness, cognitive behavioral therapy, and exercise – and make it available in community settings.

NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-19-021
Summary:

Chronic pain is common, costly, and debilitating. Opioid prescription in the treatment of chronic pain is frequent and carries a consequent risk of poor treatment outcome, as well as higher morbidity and mortality in a clinically significant number of patients, particularly those who meet criteria for opioid dependence. Despite the alarming increases in prescription opiate misuse and opioid use disorder (OUD) nationally in the United States, there are few treatment options available that target both pain-related interference and OUD among patients with chronic pain. In military veterans, this issue is of particular importance as numerous reports indicate frequent use of opioids in the treatment of chronic pain, as well as increasing opioid-related problems. To date, there are no evidence-based treatment options that aim to both reduce pain interference while simultaneously addressing problematic opioid use. The overall aim of this study will be to determine the efficacy of an integrated psychosocial treatment in veterans with chronic pain who are taking buprenorphine for the treatment of OUD. To achieve this aim, they will utilize a randomized design to assess the efficacy of two empirically supported interventions: Acceptance and Commitment Therapy for chronic pain and Mindfulness-Based Relapse Prevention for substance use and misuse.

NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010
Summary:

Cholecystokinin B receptor (CCKBR) is a molecule found in the brain that helps regulate anxiety and depression but also influences the development of tolerance to opioids. CCKBR levels are also increased in models of nerve injury-induced (neuropathic) pain. Therefore, targeting CCKBR may offer a new approach to treating neuropathic pain and the associated anxiety and depression. Researchers have developed mouse antibodies that can inactivate CCKBR. However, to be usable in humans without causing an immune response, these antibodies need to be modified to include more human sequences. This project will use a fragment of the CCKBR antibody, modify it with the addition of human antibody sequences, and then select the clones that bind most strongly and specifically to human CCKBR. These will then be tested in cell and animal models of neuropathic pain to identify the most promising candidates for further evaluation in humans.

NOFO Title: HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium - Scientific and Data Research Center (U01 Clinical Trial Required)
NOFO Number: RFA-DK-18-031
Summary:

The University of Pennsylvania Perelman School of Medicine serves as the Scientific and Data Research Center (SDRC) for the Hemodialysis Opioid Prescription Effort (HOPE) Consortium. Specifically, the SDRC will 1) provide scientific leadership for the HOPE Consortium clinical trial; 2) provide comprehensive operational support to the Clinical Centers for implementing the collaboratively designed trial protocol; 3) develop and lead a Stakeholder Engagement Working Group; 4) integrate and analyze data from the electronic health records of the participating Clinical Centers; 5) establish, promote, and maintain consortium-wide high standards for quality assurance and practices; 6) initiate and oversee contracts with industry partners; 7) prepare reports for the Data and Safety Monitoring Board, and support the preparation of Consortium reports of scientific findings; 8) prepare, document, and transfer Consortium data and biosamples to a Central Repository; and 9) develop approaches for disseminating the trial findings to diverse stakeholders.

NOFO Title: HEAL Initiative: Interdisciplinary Teams to Elucidate the Mechanisms of Device-Based Pain Relief (RM1 Clinical Trial Optional)
NOFO Number: NS22-016
Summary:

Chronic pain is a debilitating condition for which there is a pressing need for safe, effective treatments. Neurostimulation therapies that target nerve structures such as the dorsal root ganglion (DRG) and the spinal cord, have shown promising results for treating chronic pain, but researchers don’t know how they work. This project focuses on two prevailing models used to explain the therapeutic effects of neurostimulation: the gate-control model in which pain signals are blocked from reaching the brain and the T-junction filtering model in which pain signals are blocked from reaching the spinal cord. Strategies will include innovative behavioral, electrophysiological, imaging, and computational modeling techniques. The results of these studies will help explain why neurostimulation therapies work and potentially offer new treatment strategies for improved pain relief.

NOFO Title: HEAL Initiative: Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management
NOFO Number: RFA-AT-22-003
Summary:

Pain in the muscles and surrounding connective tissues (myofascial pain) can affect many regions of the body and is a key component of chronic low back pain. Patients with chronic low back pain have a range of musculoskeletal problems perpetuating their pain. There is a significant clinical need to identify the components of myofascial pain in people with chronic low back pain. Advances in ultrasound technology have allowed researchers to identify several differences in muscle and connective tissues related to myofascial pain. This project will develop and validate an ultrasound-based biomarker signature for myofascial pain in the low back. This research will also refine the biomarker signature using advanced machine learning approaches, toward future testing in in a randomized controlled clinical trial.

NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program: Phase 2 Clinical Trials (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-AR-19-029
Summary:

The chronic low back pain (cLBP) subgroup with comorbid depression or anxiety disorders, known as high negative affect (NA), needs better non-opioid, comprehensive pain treatment options. Data shows that the combination of antidepressants (AD) and fear avoidance physical therapy is more efficacious at improving pain, function, depression, and anxiety in cLBP patients with high NA than each treatment alone or a control condition. Research also finds that an enhanced fear avoidance rehabilitation protocol (EFAR; fear avoidance-based physical therapy, pain education, and motivational messaging) further improves outcomes. To address the unmet needs of cLBP patients with high NA, this study will test in a randomized trial whether the combination of AD and EFAR is more effective than each treatment alone at relieving pain, improving function, combating depression, and preventing opioid misuse. This multimodal combination approach of pharmacotherapy and behavioral therapy is novel to the field and has the potential to shift current treatment paradigms.

NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003
Summary:

The research team developed an in vitro multi-component joint on a chip (microJoint), in which engineered osteochondral complexes, synovium, and adipose tissues were integrated. This study will introduce sensory innervation into the microJoint and a neuron-containing microfluidic ally will be developed to innervate the microJoint. The osteoarthritis (OA) model will be created in the Neu-microJoint system. The research team will assess activation and/or sensitization of nociceptive afferents with electrophysiology, as well as neurite outgrowth. They will mechanically insult the Neu-microJoint and assess the emergence of “pain” in response to prolonged mechanical stress. Researchers will assess the impact of drugs used clinically for management of OA on OA models and will then use “omic” approaches to identify new biomarkers and therapeutic targets. Researchers will assess the impact of opioids—which they hypothesize will increase the rate of joint degeneration and potentiate the release of pain-producing mediators—on neural activity in the presence and absence of joint injury, as well as the integrity of all joint elements.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

Medications have proven to be effective for treating opioid use disorder (OUD). Increasing accessibility to buprenorphine provides an opportunity for many with OUD to benefit from its proven effectiveness. Adherence to medication-based treatments however is low, in part because of the stigma associated with use of this and other effective drugs and as such, leads to inadequate treatment and poor outcomes. This study aims to understand the effects of stigma on patient engagement, retention, and outcomes of buprenorphine treatment. Knowledge drawn from the HIV Stigma Theory and tools developed to reduce HIV associated stigma will be used to assess OUD stigma and to develop interventions to reduce it in the context of buprenorphine treatment. The study findings may provide resources to address stigma and thus maximize treatment adherence among those affected by OUD.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107
Summary:

Identifying optimal chronic low back pain treatments on a patient-specific basis is an important and unresolved challenge. Tailoring interventions according to patient movement characteristics is one option. This research is characterizing patients based on spinal motion during functional tasks and daily activities and will use artificial intelligence to objectively characterize motions of the spine during both clinical assessments and day-to-day life. During clinical assessments, participants will be asked to perform functional tasks while wearing motion sensors. Data collected from the sensors will be used to identify tasks of interest, such as activities of daily living and aberrant/painful motions. An artificial intelligence approach will then interpret data collected continuously during assessment in patients’ homes over a 7-day testing period. Ultimately, this data could be used to help clinicians tailor treatments that are responsive to a patient’s real-world functional impairments.

NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Chronic visceral pain disorders, such as interstitial cystitis/bladder pain syndrome, are among the most difficult types of pain to treat. This project will conduct a detailed analysis of an enzyme thought to be involved with the disorder (purine nucleoside phosphorylase, or PNPase) as a target for new nonopioid pain medications to treat interstitial cystitis/bladder pain syndrome. The research will lay the groundwork for developing targeted treatments for visceral pain disorders.