Funded Projects

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: Mechanisms, Models, Measurement, & Management in Pain Research (R01)
NOFO Number: PA-13-118
Summary:

Chronic pain diminishes the quality of life for millions of patients, and new drugs that have better efficacy and/or fewer side effects are needed. A promising target is the sphingosine-1-phosphate (S1P) receptor system, which mediates central nervous system (CNS) neuromodulatory functions. FTY720-phosphate, the active metabolite of FTY720 (FTY), acts as an agonist at four of the five S1P receptors (S1P1, 3, 4, 5). We propose that the S1P1 receptor is a target for treatment of neuropathic pain. We will test whether S1P1 receptors mediate anti-hyperalgesic effects in a mouse neuropathic pain model. The specific aims are to: 1) determine the role of S1P1Rs in alleviation of neuropathic pain by S1PR ligands; 2) determine the role of FTY-induced S1PR adaptation in FTY-mediated reversal of neuropathic pain; and 3) determine the role of S1P and S1P1 receptors in spinal glia in CCI-induced neuropathic pain and its reversal by FTY.

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:

The Acute to Chronic Pain Signatures (A2CPS) Program aims to identify combinations of biomarkers that predict susceptibility or resilience to the development of chronic pain. This career enhancement award will help a promising postdoctoral trainee gain access to tools and develop skills needed to pursue a career in clinical pain research. The research involves conducting collaborative multi-site cohort studies and analyzing A2CPS data to determine if a combination of metabolic and psychosocial biomarkers can be used to explain pre-surgery differences in pain, function, and disability in patients with severe knee osteoarthritis.

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 a need for safe, effective, well- tolerated drugs to treat painful neuropathy by halting or reversing the underlying pathology of the disease. One promising approach to treating painful neuropathy without opioids is the use of ghrelin, a 28-amino acid acylated peptide hormone. However, it has a short half-life and must be delivered via a constant intravenous infusion to have a therapeutic effect. Extend Biosciences' D-VITylation platform technology is truly enabling for small peptide-based therapeutics that are rapidly cleared from the bloodstream by renal filtration. The platform harnesses the naturally long half-life of vitamin D and its dedicated binding protein, VDBP. When the vitamin D molecule is conjugated to a biological therapeutic, it dramatically improves the half-life and bioavailability of the drug. Use of the technology should also allow the drug to be self-administered by subcutaneous injection. This would be of significant benefit to patients. In this project, the team will test the efficacy of EXT405 in a cell-based model of neuropathy as well as in animal models of CIPN and diabetes- induced neuropathy.

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

The University of Pittsburgh Low Back Pain: Biological, Biomechanical, and Behavioral Phenotypes (LB3P) Mechanistic Research Center (MRC) will to perform in-depth phenotyping of patients with chronic low back pain (cLBP), using a multimodal approach to characterize patients and provide insight into the phenotypes associated with experience of cLBP to direct targeted and improved treatments. The LB3P MRC will be formed of three Research Cores, three support cores, and one research project. This approach will leverage and integrate distinctive resources at the University of Pittsburgh laboratories to deliver quantified biomechanical, biological, and behavioral characteristics; functional assessments; and patient-reported outcomes, coupled with advanced data analytics using a novel Network Phenotyping Strategy (NPS). By eliminating isolated and disconnected approaches to treatment and focusing on personalized patient-centric approaches, this approach will yield improved outcomes and patient satisfaction.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

Digital health interventions, such as virtual reality (VR) applications, have become available for the treatment and monitoring of numerous health conditions, including pain management. A current HEAL-funded study is evaluating the role of a therapeutic VR approach for chronic low back pain. However, racial and ethnic disparities exist in patient access and response to such VR applications, as well as in the incidence and reporting of pain. For example, non-Hispanic Blacks and Hispanics are more likely to report severe pain than non-Hispanic Whites, yet are less likely to have access to digital health information and interventions. To address these disparities, this project will develop a framework to advance diversity and inclusion in digital health trials and will seek to increase the proportion of non-Hispanic Black and Hispanic participants in the ongoing VR trial by tailoring recruitment materials and using novel artificial intelligence-driven cohort building tools.

NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development Initial Translational Efforts [Small Molecules and Biologics] (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-21-016
Summary:

Disruptions in make-up of the microbiome are associated with disorders characterized by chronic pain and inflammation, such as rheumatoid arthritis and fibromyalgia. The gut microbiome has immune and metabolic effects, and human gut-derived bacteria may be a source of novel, safe, and non-addictive pain treatments. However, connections between gut and pain signals, known as the “gut–pain axis,” are still poorly understood. This study aims to identify human-gut-native bacteria that i) interact with known pain targets in lab studies, ii) test their activity and analgesic/anti-inflammatory potential in an animal model, and iii) develop a computational approach to predict microbial-genetic effects on pain signals.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Identification of new targets and mechanisms underlying chronic neuropathic pain is essential for the discovery of novel treatments and preventative tactics for better neuropathic pain management. A recent exploration of next-generation RNA sequencing identified a large, native, full-length long noncoding RNA (lncRNA) in mouse and human dorsal root ganglion (DRG). It was named as nerve injury-specific lncRNA (NIS-lncRNA), since its expression was found increased in injured DRGs, in response to peripheral nerve injury, but not in response to inflammation. Preliminary findings revealed that blocking the nerve injury-induced increases in DRG NIS-lncRNA levels ameliorated neuropathic pain. This project will validate NIS-lncRNA as a therapeutic target in animal models of neuropathic pain and in cell-based functional assays utilizing human DRG neurons. Completion of this proposal will advance neuropathic pain management and might provide a novel, non-opioid pain therapeutic target.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
NOFO Number: PA-18-575
Summary:

Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves, but no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, the team will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing pain.  

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

As many as 64% of patients with Temporomandibular Joint Disorders (TMJDs) report symptoms consistent with Irritable Bowel Syndrome (IBS). However the underlying connection between these comorbid conditions is unclear and treatment options are poor. As such, pain management for these Chronic Overlapping Pain Conditions (COPCs) is a challenge for physicians and patients. This project will determine whether the convergence of pain from different peripheral tissues and perceived stress occurs in the brain and elicits a change in central neural processing of painful stimuli. This project will identify and validate specific lipids, enzymes and metabolic pathways that change expression in the brain during the transition from acute to chronic overlapping pain that can be therapeutically targeted to treat COPCs. Multi-disciplinary approaches will be used to combine brain imaging, visualization of spatial distribution of molecules, genetics, pharmacological and behavioral research techniques.

NOFO Title: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-010
Summary:

Although opioid-based analgesics have been proven effective in reducing the intensity of pain for many neuropathic pain conditions, their clinical utility is grossly limited due to the substantial risks involved in such therapy, including nausea, constipation, physical dependence, tolerance, and respiratory depression. Cumulative evidence suggests that human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain with limited side effects due to its restricted expression in nociceptors within the peripheral nervous system; however, direct activation of MRGPRX1 at peripheral terminals is expected to induce itch side effects, limiting the therapeutic utility of orthosteric MRGPRX1 agonists. This finding led to the exploration of positive allosteric modulators (PAMs) of MRGPRX1 to potentiate the effects of the endogenous agonists at the central terminals of sensory neurons without activating peripheral MRGPRX1. An intrathecal injection of a prototype MRGPRX1 PAM, ML382, effectively attenuated evoked, persistent, and spontaneous pain without causing itch side effects. The goal of this study is to develop a CNS-penetrant small-molecule MRGPRX1 PAM that can be given orally to treat neuropathic pain conditions.