Funded Projects

The HEAL Initiative is establishing a HEAL Data Ecosystem to help investigators manage and share HEAL-generated data, and quickly and efficiently disseminate HEAL results broadly to stakeholders. The HEAL Platform, built by the University of Chicago, will enable broad sharing of HEAL data by linking data stored in various locations, annotated and curated to various extents, to one central interface where studies, data, and digital assets can be discovered and accessed via metadata query. The Platform will also provide secure workspaces so that under appropriate conditions, data can be pulled from disparate repositories and computed on in the same cloud space, using tools and analytic suites provided within. The Platform team will collaborate closely with the HEAL Data Stewardship Group (Renascence Computing Institute at the University of North Carolina Chapel Hill and RTI, International) to meet the needs and goals of the HEAL Data Ecosystem.

The HEAL Initiative is establishing a HEAL Data Ecosystem to help investigators manage and share HEAL-generated data. A key principle underlying the HEAL Data Ecosystem strategy is to make those data findable, accessible, interoperable, and reusable (FAIR). Renascence Computing Institute at the University of North Carolina Chapel Hill (RENCI) and RTI, International (RTI) [RENCI/RTI] are serving as the HEAL Data Stewardship Group to guide HEAL investigators as they prepare their data to connect to the HEAL Platform, a secure data access and computing environment that will leverage metadata query to provide access to data and digital assets stored in various disparate repositories. The HEAL Data Stewardship Group is engaging HEAL investigators to understand and enhance data management needs, provide tools, training, and best practices for making data FAIR, and understand and support valuable uses and reuses of HEAL data sharing via the Platform The HEAL Data Stewardship Group will collaborate closely with the HEAL Platform team at the University of Chicago to meet the needs and goals of the HEAL Data Ecosystem.

Chronic musculoskeletal pain is common and often severe enough to be disabling. Some treatments such as cognitive behavioral therapies or analgesics may relieve pain for some, but not all patients. Combining effective therapies and providing support to ensure that patients are motivated to adhere to their treatment may prove to be more beneficial to patients than prescribing a drug or recommending a single non-pharmacological treatment. This study aims to evaluate a combination of complementary treatments and Registered Nurse (RN) support to motivate patients to use and maintain combined therapies. Some patients will receive phone-based motivational interviews with an RN to enhance their adherence to pain coping skills learned through web-based cognitive behavioral therapy in combination with duloxetine, a pain-relieving drug. Others will receive both treatments but will not receive support from an RN. The study aims to determine whether motivational nursing support enhances adherence to newly learned pain coping skills, and results in improved pain relief and physical function.

Opioid overdose deaths disproportionately affect Black individuals in the United States. While the use of complementary and integrative pain treatments is effective and widely recommended, Black pain patients (especially those who also have depression) face barriers to the use of these approaches. This project will refine, test, and prepare to implement a novel approach to overcoming these treatment barriers. The research will partner with and empower Black patients to find safe, effective pain treatments that best match their values, preferences, and lifestyles.

This project addresses the significant challenge of providing evidence-based, non-pharmacologic pain management to veterans with chronic pain living in rural regions. This research will test whether an innovative, virtual complementary and integrative group-based treatment will improve rural veterans’ pain management, function, and well-being. The research will also devise, evaluate, and adapt strategies for implementing this intervention while working with the health care system, veteran patients, and communities. The scalable, 12-week intervention includes pain education, mindfulness, pain-specific exercises, and cognitive behavioral strategies.

Chronic pain affects over 100 million Americans, costing society about $600 billion annually. Despite numerous pharmacological and non-pharmacological therapies, over 50% of chronic pain sufferers feel little control over their pain. CognifiSense has developed a patent-pending Virtual Reality Psychological Therapy (VRPT), which is designed to create lasting reduction of chronic pain by addressing the maladaptive learning processes driving pain chronification. VRPT is an experiential learning system, which provides the brain a new set of signals that teaches it that the pain is not as bad as it perceived and that it has greater control over the pain than it perceived. VRPT combines the immersive power and the ability to individualize the therapy of Virtual Reality with well-researched principles of self-distancing, self-efficacy, and extinction to retrain the brain. The goal of this study is to determine the clinical feasibility of VRPT in achieving a lasting reduction of chronic pain, establish brain mechanisms associated with treatment response, and collect comprehensive user feedback to enable further refinement of the current product prototype. CognifiSense's VRPT has the potential to be a significant clinical and business opportunity in the treatment of chronic pain.

Migraines and other headaches are often debilitating for patients, yet few treatment options providing sustained relief exist. All available therapies, including frequently prescribed opioids, have considerable side effects or limitations. Therefore, novel treatment approaches are needed to reduce or eliminate the need to use opiates and other systemic pharmaceuticals. Thermaquil Inc. has developed a new way of stopping migraine and other headache pain by noninvasively blocking pain signal transmission in the head, which in initial studies allowed patients to discontinue use of opioids and other addictive pain medications. Thermaquil will now be conducting a larger randomized controlled trial to demonstrate the safety and effectiveness of this novel approach. After a baseline period, patients will be randomly assigned to the active or control condition and receive a single treatment. The study will continue for 12 weeks with the active versus control arms, before all patients will be given active therapy for an additional 12 weeks.

Many non-opioid drugs target G Protein-Coupled Receptors (GPCRs), a family of proteins involved in many pathophysiological processes including pain, fail during clinical trials for unknown reasons. A recent study found GPCRs not only function at the surface of nerve cells but also within a cell compartment called the endosome, where their sustained activity drives pain. This study will build upon this finding and test whether the clinical failure of drugs targeting plasma membrane GPCRs is related to their inability to target and engage endomsomal GPCRs (eGPCRs). This study will use stimulus-responsive nanoparticles (NP) to encapsulate non-opioid drugs and selectively target eGPCR dyads to investigate how eGCPRs generate and regulate sustained pain signals in neuronal subcellular compartments. This study will also validate eGCPRs as therapeutic targets for treatment of chronic inflammatory, neuropathic and cancer pain. Using NPs to deliver non-opioid drugs, individually or in combinations, directly into specific compartments in nerve cells could be a potential strategy for new pain therapies.

An important component of neuropathic pain is spontaneous or ongoing pain, such as burning pain or intermittent paroxysms of sharp and shooting pain, which may result from abnormal spontaneous activity in sensory nerves. However, due to technical limitations, spontaneous activity in sensory neurons in vivo has not been well studied. Using in vivo imaging in genetically-modified mice, preliminary findings identified spontaneously-firing clusters of neurons formed within the dorsal root ganglia (DRG) after traumatic nerve injury that exhibits increased spontaneous pain behaviors. Furthermore, preliminary evidence has been collected that cluster firing may be related to abnormal sympathetic sprouting in the sensory ganglia. This project will test the hypothesis that cluster firing is triggered by abnormal sympathetic inputs to sensory neurons, and that it underpins spontaneous paroxysmal pain in neuropathic pain models. Findings from this project will identify potential novel therapeutic targets for the treatment of neuropathic pain.

Neuropathic pain is a debilitating and complex medical condition for which safe and non-addictive treatment options are urgently needed. Preliminary studies have found that lysophosphatidic acid receptor 5 (LPA5) is present in areas of the body that signal pain, including at high levels in rodent models of neuropathic pain. This project will use genetic and pharmacological approaches to determine whether blocking LPA5 signaling reduces neuropathic pain toward future testing in humans.  

Chronic pain is a major health burden associated with immense economic and social costs. Predictive biomarkers that can identify individuals at risk of developing severe and persistent pain, which is associated with worse disability and greater reliance on opioids, would promote aggressive, early intervention that could halt the transition to chronic pain. The applicant’s team uncovered evidence of a unique cortical biomarker signature that predicts pain susceptibility (severity and duration). This biomarker signature could be capable of predicting the severity of pain experienced by an individual minutes to months in the future, as well as the duration of pain (time to recovery). Analytical validation of this biomarker will be conducted in healthy participants using a standardized model of the transition to sustained myofascial temporomandibular pain. Specifically the biomarker signature will be tested for its ability to predict an individual’s pain sensitivity, pain severity, and pain duration and will perform initial clinical validation.

A more thorough understanding of neuropathic pain is critical for developing new target-specific medications. Researchers know that peripheral nerve injury changes various cell processes that affect two ion channels linked with chronic pain. Preliminary studies indicate that molecular changes known as phosphorylation to the collapsin response mediator protein 2 (CRMP2), one of five intracellular phosphoproteins, promotes abnormal excitability in the brain region that contributes to neuropathic pain. This project aims to develop small molecule inhibitors of CRMP2 phosphorylation as potential therapeutics for pain.