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.

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.

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.

A current obstacle to developing more effective therapies for chronic low back pain is the lack of clinical trials assessing the feasibility and potential effectiveness of promising new targets for neuromodulation. This project will explore the feasibility of using deep brain stimulation of a new brain target for treating chronic low back pain. The study will also explore imaging biomarkers in patients with chronic low back pain that can be used to predict whether someone is a candidate or may respond to deep brain stimulation therapy, to guide programming and patient selection for this therapy in the future.

Complex regional pain syndrome is one of the most disabling and difficult-to-treat chronic pain conditions. This project seeks to develop a novel, biological treatment for the condition using injected human bone marrow cells. that can form and repair skeletal tissues and control nervous and immune system activity. The research will determine the dose and source of clinical-grade bone marrow cells needed, toward the goal of submitting an Investigational New Drug Application to the U.S. Food and Drug Administration that will enable further clinical study.

Spinal cord injury (SCI) impairs sensory transmission and leads to chronic, debilitating neuropathic pain. While our understanding of the development of chronic pain has improved, the available therapeutics provide limited relief. We will examine the peripheral immune and inflammatory response. Secondary inflammation in response to SCI is a series of temporally ordered events: an acute, transient upregulation of chemokines, followed by the recruitment of monocytes/macrophages and generation of an inflammatory environment at the lesion site in the spinal cord, but also surrounding primary nociceptors in the dorsal root ganglia (DRG). These events precede neuropathic pain development. Previous work indicates that after SCI, macrophage presence in the DRG correlates with neuropathic pain. We propose to study: 1) whether the phenotype of macrophages that infiltrate the DRG is different than those that persist chronically after SCI and 2) how manipulation of macrophage phenotype affects nociceptor activity and pain development.

Pain is a major problem for spinal cord injury (SCI) patients that tends to persist and even worsen with time. No treatments are currently available to consistently relieve pain in SCI patients. This study will investigate the feasibility of Epidural Electrical Stimulation (EES) using the Abbott Proclaim? SCS system with two electrodes to treat neuropathic pain in patients with thoracic spinal cord injury. In this double-blind, prospective, randomized clinical trial, patients with subacute, traumatic, complete thoracic SCIs with American Spinal Injury Association (ASIA) Impairment Scale A will be randomized to receive either ?EES on? (treatment intervention) or ?EES off? (control intervention) of the target regions for pain control (lead overlying the spinal cord anatomy corresponding with their pain distribution) and neurorestoration (lead overlying the conus medullaris) as an adjunct to physical therapy. This study will help determine whether EES can help patients with SCI neuropathic pain and have more widespread clinical applicability.

TWIK-related spinal cord K+ (TRESK) channel is abundantly expressed in all primary afferent neurons (PANs) in trigeminal ganglion (TG) and dorsal root ganglion (DRG), mediating background K+ currents and controlling the excitability of PANs. TRESK mutations cause migraine headache but not body pain in humans, suggesting that TG neurons are more vulnerable to TRESK dysfunctions. TRESK knock out (KO) mice exhibit more robust behavioral responses than wild-type controls in mouse models of trigeminal pain, especially headache. We will investigate the mechanisms through which TRESK dysfunction differentially affects TG and DRG neurons. Based on our preliminary finding that changes of endogenous TRESK activity correlate with changes of the excitability of TG neurons during estrous cycles in female mice, we will examine whether estrogen increases migraine susceptibility in women through inhibition of TRESK activity in TG neurons. We will test the hypothesis that frequent migraine attacks reduce TG TRESK currents.

This project aims to develop and clinically validate a 64-channel spinal cord stimulation therapy for treating chronic neuropathic pain of the lower extremities, groin, and lower back. With an increased channel count and the ability to precisely target medial and lateral structures of the spinal cord, the system will treat chronic pain with greater efficacy and reduced side effects. This project will pursue a safe, effective, and non-addictive treatment for neuropathic pain through the testing of enhanced HD64 active leads to be manufactured under GMP regulations. The leads will then undergo electrical, mechanical, biocompatibility, and sterilization testing before being tested in a 10-subject early feasibility study.