Funded Projects

NOFO Title: Arts-Based Approaches in Palliative Care for Symptom Management (R01)
NOFO Number: PAR-14-294
Summary:

This study addresses the public health problem of chronic pain as one of the most feared symptoms in people with cancer. Insufficient relief from pharmacological treatments and the fear of side effects are important reasons for the growing use of complementary pain management approaches in people with cancer. One such approach is music therapy. Although efficacy of music therapy for pain has been established, there are no mechanistic studies clarifying how it works in clinical populations. The overarching goals of this study are to 1) examine mediators and moderators hypothesized to account for the pain-reducing effects of interactive music therapy (IMT) in people with advanced cancer and chronic pain and 2) validate IMT’s theory of action. The results of this study will provide estimated effects sizes of IMT on the mediators and preliminary effect size estimates for the pain outcomes. This information will be instrumental in the development of a subsequent large-scale efficacy trial.

NOFO Title: Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Required)
NOFO Number: PA-20-193
Summary:

Enhancing the workforce of pain investigators and practitioners is a key goal of the NIH HEAL Initiative. This mentoring award will allow a selected investigator to train early career investigators in patient-oriented research focusing on the development of diagnostic and prognostic biomarkers for high-impact chronic pain. Mentoring activities will include training in designing and implementing pain research studies, preparing scientific papers and presentations, writing successful grant applications, the responsible conduct of research, and successful navigation of the academic process to achieve scientific independence. This training will allow mentees to advance their independent careers as pain researchers.

NOFO Title: Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Required)
NOFO Number: PA-20-193
Summary:

The HEAL-funded Sequenced-strategy for Improving Outcomes in People with Knee Osteoarthritis Pain (SKOAP) clinical trial evaluates behavioral, pharmacologic, and procedural interventions for patients with knee osteoarthritis pain. It is designed to mimic clinical care for these patients by first testing the effectiveness of conservative and nonsurgical interventions before considering surgical interventions. It is a large-scale clinical trial with a novel design that evaluates multidisciplinary treatments. Therefore, it offers a unique training opportunity for junior investigators from various disciplines who are interested in pain research and management. This mentoring award will allow a selected investigator to train junior investigators by providing protected, mentorship-focused time.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

There is an unmet need for an effective parenteral/oral analgesic for acute post- operative pain management without the risks of opioid addiction. Salsalate, a dimer or salicylic acid, is currently available in oral dosage for the treatment of osteoarthritis and rheumatoid arthritis. Salsalate works at multiple levels to target multiple steps along the surgical pain pathway. Salsalate through its active metabolite, salicylic acid (SA), reduces NF-?B activation via IKK-kinase beta inhibition, and has no direct binding to cyclooxygenase 1 (Cox-1); therefore, does not affect function of platelets, resulting in a safer hematological and gastrointestinal safety profile. RH Nano proposes a plan for manufacturing and pre- clinical testing of parenteral M-salsalate in two animal models to assess the efficacy and safety in the treatment of acute postoperative pain management. In this proposal, the team will develop the optimal formulation under strict Chemistry Manufacturing and Control guidelines. In Phase II, the team proposes to conduct the pharmacokinetics and toxicology studies of M-salsalate in two species of animals (rodent and non-rodent). Additionally, the project will use an animal pain model for preclinical efficacy studies, and an in vivo Receptor Occupancy assay in animal brain tissues to assess the opioid sparing properties of M-salsalate. 

NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

G-protein coupled receptor 3 (GPR3) is an orphan receptor present in the central nervous system (CNS) that plays important role in many normal physiological functions and is involved in a variety of pathological conditions. Although the brain chemical that activates this receptor has not been identified, work with GPR3 knockout mice has identified GPR3 as a novel drug target for several Central Nervous System (CNS) mediated diseases including neuropathic pain. However, despite the emerging behavioral implications of the GPR3 system, little is known about how GPR3 affects behavior due to the lack of potent and selective chemical probes that allow scientists to examine functioning of the receptor. Recently, two cannabinoid chemicals present in the cannabis plant were discovered as affecting GPR3. This study will modify the chemical structure of these compounds to increase their potency and selectivity so that they may be used as pharmacological tools to investigate the role of GPR3 in modulating pain. In addition, this project focuses on identifying new compounds that show promise for development into therapeutics for the treatment of pain.

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 tissue (myofascial pain) is a significant health concern affecting hundreds of millions of Americans. Understanding and managing myofascial pain has been limited due to a lack of tools to help clinicians diagnose and treat this disorder. While past efforts to understand myofascial pain have focused on impairments in how connective tissues connect to other tissues in the body, this project will use a new imaging technique to study myofascial tissue physical properties, including how they move in the body and their structural stiffness. This research will identify an imaging biomarker to be used in a randomized controlled clinical trial to predict patient responses to a myofascial pain treatment.

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:

This project will build overdose models for fentanyl, methadone, codeine, and morphine in a multi-organ system and evaluate the acute and repeat dose, or chronic effects, of overdose treatments as well as off-target toxicity. Researchers developed a system using human cells in a pumpless multi-organ platform that allows continuous recirculation of a blood surrogate for up to 28 days. They will develop two overdose models for male and female phenotypes based on pre-B?tzinger Complex neurons and will integrate functional immune components that enable organ-specific or systemic monocyte actuation. Models for cardiomyopathy and infection will be utilized. Researchers will establish a pharmacokinetic/pharmacodynamic model of overdose and treatment to enable prediction for a range of variables. We will use a serum-free medium with microelectrode arrays and cantilever systems integrated on chip that allow noninvasive electronic and mechanical readouts of organ function.

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 tissue (myofascial pain) is a significant health concern affecting hundreds of millions of Americans.  Myofascial pain is primarily diagnosed by asking people about their amount of pain as well as through a physical examination. Both approaches are imprecise ways to diagnose the specific type of pain a patient is experiencing and what is causing it. This project aims to improve myofascial pain management and treatment by developing ways to measure changes to soft tissues (e.g., muscle, connective tissues, nerves, blood vessels) in people with myofascial pain compared with soft tissues in people who are not in pain. The project will develop an imaging biomarker that can distinguish healthy and diseased soft tissues that may contribute to myofascial pain syndrome. The project will then test the ability of these biomarkers to predict patient outcomes in a randomized controlled clinical trial.

NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Temporomandibular joint (TMJ) disorders are the most common form of chronic pain in the face and mouth area (orofacial pain), but relatively little is known about the biological causes of these conditions. This project will define the properties of sensory neurons that connect to tissues that make up the TMJ which connects the lower jaw and skull. This research aims to lay groundwork for development of new therapeutic approaches to treat these painful conditions.

NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Pain caused by degenerative joint diseases such as osteoarthritis (OA) is a major public health challenge that significantly affects quality of life for millions of Americans. There are no therapies available that offer pain relief and reverse the course of OA.  This project will use state-of-the-art technologies to create a neuronal connectivity and molecular map of the mouse knee joint, which will help identify molecular signatures that can be targeted for therapy. The research will include animals of different ages and of both sexes and test joint effects after exercise, in animals with OA, and after gene therapy that delivers an experimental OA medication directly to the joint.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

There is an urgent need for non-opioid post-operative pain management solutions.  This research is developing a naturally absorbable polymer film that can release controlled amounts of the non-opioid analgesic bupivacaine – aiming to manage pain for several days following surgery. Project objectives are to optimize the timing of drug release, develop manufacturing standards, determine effective dosage for preserving motor function, and determine safety and efficacy in mouse models of neuropathic pain. Continued development of this film delivery system may lead to a new, non-opioid therapeutic strategy that could be combined with local anesthesia for up to 4 days after surgery to reduce or potentially eliminate opioids use.

NOFO Title: HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) (UG3/UH3, Clinical Trials Optional)
NOFO Number: RFA-AT-20-004
Summary:

Back pain is the most common chronic pain diagnosis and the most common diagnosis for which opioids are prescribed. Clinical practice guidelines make it clear that nonpharmacologic treatments are preferable to opioids for patients with back pain. Despite clear evidence, over-prescribing of opioids to individuals with back pain continues. Providers of nonpharmacologic care are often absent or unreachable from rural and low-income communities and patients with limited financial resources. Many rural and low-income communities are served by Federally Qualified Health Centers (FQHCs) that are at the forefront of the opioid crisis, but often lack adequate options to provide accessible nonpharmacologic treatments. This pragmatic clinical trial will compare the effectiveness of different telehealth strategies to provide effective nonpharmacologic interventions to overcome the barriers specific to serving rural and low-income communities. The trial will evaluate two strategies, one providing both a brief pain teleconsult with phone-based physical therapy, the other uses an adaptive strategy ? providing the brief pain teleconsult first, followed by phone-based physical therapy to those who need additional treatment. The study will also evaluate outcomes related to the efforts to implement strategies in FQHC clinics. This research will provide a toolkit for future efforts to make nonpharmacological interventions for back pain available in other low resource health care settings.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

Some chemotherapy treatments damage nerves outside the brain and spinal cord. This condition, chemotherapy-induced peripheral neuropathy, involves tingling, burning, weakness, or numbness in hands and/or feet and affects nearly 70% of cancer patients receiving chemotherapy. Common pain medications, including opioids, can relieve pain for short intervals but are not suitable for long-term therapy. This project will conduct studies to investigate the safety and tolerability of a novel strategy to treat neuropathic pain: modifying the activity of the dorsal root ganglia, which are nerve cells in the spinal cord that communicate pain signals to and from the brain.