Funded Projects

While traditional epidural spinal cord stimulation (SCS) for intractable pain has been very efficacious for the patients responsive to it, the success rate has held at approximately 55%. Dorsal root ganglion (DRG) stimulation has shown promise in early trials to provide greater pain relief. Although the decrease in back pain at 3 months was significantly greater in the DRG arm vs. SCS, the adverse event rate related to the device or implant procedure was significantly higher in the DRG arm. Researchers will develop the “Injectrode” system to make the procedure simpler and safer by using an alternative to implantation: using an injectable pre-polymer liquid composite that cures quickly after injection adjacent to the DRG. They will compare an Injectrode-based system with traditional electrode stimulation at the DRG as an alternative to opioid administration. Researchers will perform benchtop characterization and refinement as a precursor to a clinical study, use modeling and animal testing to refine the efficiency of energy transfer from a transcutaneous electrical nerve stimulation unit to an Injectrode/Injectrode collector concept, and optimize the procedure for the complex anatomy of the human DRG.

This project aims to develop a next-generation noninvasive neuromodulation system for non-addictive pain treatments. The research team will build an integrated system that uses magnetic resonance image-guided focused ultrasound (MRgFUS) stimulation to target pain regions and circuits in the brain with high precision. The system will use MR imaging to locate three pain targets commonly used in clinical pain treatments, to stimulate those targets with ultrasound, and to monitor responses of nociceptive pain circuits using a functional MRI readout. Three collaborating laboratories will tackle the goals of this project: (Aim 1) Develop focused ultrasound technology for neuromodulation in humans, compatible with the high magnetic fields in an MRI scanner. (Aim 2) Develop MRI technology to find neuromodulation targets, compatible with focused ultrasound transducers. (Aim 3) Validate the complete MRgFUS neuromodulation system in brain pain regions in nonhuman primates. By the end of the project, the research team will have a fully developed and validated MRgFUS system that is ready for pilot clinical trials in pain management.

Researchers will develop a novel transcranial focused ultrasound (tFUS) device for pain treatment and establish its effectiveness for treating sickle cell disease (SCD) pain in humanized mice. The tFUS will target the specific cortical regions involved in SCD pain using a novel non-invasive electrophysiological source imaging technique. The project’s goals have several aims. Aim 1: Develop tFUS devices for pain treatment. The mouse-scale system will be designed to validate the therapeutic effect of stimulating the anticipated cortical targets. This will inform development of the simpler human-scale system, which will use models of the skull to select cost-effective transducers to reach the targets. Aim 2: Evaluate tFUS effectiveness and optimize stimulation parameters in an SCD mice model. Researchers will determine effective tFUS parameters to chronically reduce SCD pain in mice and validate this using behavioral measures. Aim 3: Use electrophysiological source imaging to target and trigger closed-loop tFUS in animal models. This aim also includes performing safety studies to prepare for human trials. The project will develop a transformative, noninvasive tFUS device to effectively and safely treat pain in SCD. 

Approximately 3.6 million Americans live with an amputated extremity, and the majority of these individuals are likely to suffer from chronic post-amputation pain. There is no consensus as to a recommended therapy for such pain, and many treatments do not provide sufficient pain control. Some studies have shown effective pain suppression from delivering an anesthetic agent directly to an injured nerve. This research aims to develop a device that can be implanted near the injured nerves of an amputated limb to deliver an anesthetic. Findings from this preclinical study will optimize design and delivery features to maximize its effect on pain control for as long as possible without needing a drug refill. The research is expected to advance eligibility for further testing in large animals and humans.

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.

Opioids are widely used pain treatments, despite their relative ineffectiveness for chronic pain and their high potential for misuse and addiction. There is thus an urgent need for alternative, non-addictive pain treatments. Genetic and functional studies of human pain disorders and animal models of pain have validated Nav1.7, a voltage-gated sodium channel as an attractive target for new pain treatments. Currently available blockers of these channels can sometimes provide symptomatic relief for patients but have worrisome side effects affecting the brain and heart. This study aims to develop and validate an innovative site-directed RNA editing strategy that will offer the ability to create new versions of molecules to block Nav1.7, toward establishing a novel, non-addictive approach to treat chronic pain.

This project will identify molecular characteristics of human sensory neurons and non-neuronal cells from the human dorsal root ganglia. This structure located outside the spinal cord is integrally involved in communicating pain signals to and from the brain. The research will use molecular approaches to characterize tissues obtained from organ donors and in patients who experience chronic pain. The findings will also help generate a connectivity map, or “connectome,” of nerve cell connections between the dorsal root ganglia of the spinal cord and the brain.

The BACPAC Research Program’s Data Integration, Algorithm Development, and Operations Management Center (DAC) will bring cohesion to research performed by the participating Mechanistic Research Centers, Technology Research Sites, and Phase 2 Clinical Trials Centers. DAC Investigators will share their vision and provide scientific leadership and organizational support to the BACPAC Consortium. The research plan consists of supporting design and conduct of clinical trials with precision interventions that focus on identifying the best treatments for individual patients. The DAC will enhance collaboration and research progress with experienced leadership, innovative design and analysis methodologies, comprehensive research operations support, a state-of-the-art data management and integration system, and superior administrative support. This integrated structure will set the stage for technology assessments, solicitation of patient input and utilities, and the evaluation of high-impact interventions through the innovative design and sound execution of clinical trials, leading to effective personalized treatment approaches for patients with chronic lower back pain.

The NIH’s HEAL Initiative aims to support collaboration between clinical research experts in academia and industry to accelerate the development of highly efficacious, nonaddictive analgesics for well-defined chronic pain syndromes. The University of Rochester (UR), and its leadership for the UR Hub and Spokes within Early Phase Pain Investigation Clinical Network (EPPIC-Net), will recruit subjects with a broad range of pain conditions, with a focus on leveraging clinical trial infrastructure to support patient recruitment and retention, timely and accurate data entry, and regulatory documentation, as well as recruit additional Spoke sites through a national network of analgesic researchers.

The Data Coordinating Center (DCC) of the Early Phase Pain Investigation Clinical Network (EPPIC-Net) will be the data and biospecimen manager for pain research within the HEAL Partnership. As such, it will host, manage, standardize, curate, and provide a sharing platform for data and biospecimens for HEAL initiatives, such as the Acute to Chronic Pain Signatures initiative and the BACPAC, in addition to EPPIC-Net studies. The DCC will develop and maintain a databank for depositing data, will link these data with a repository for biological samples, and will create a platform for teams to work together to analyze and interpret data. Further, the DCC will provide leadership in the statistical design and analysis of EPPIC-Net studies and will deploy advanced systems and processes for data collection, management, quality assurance, and reporting. The DCC will create, sustain, and continually advance a robust organization for the rapid design, implementation, and performance of high-quality rigorous Phase II clinical trials to test promising therapeutics for pain.

The Greater New York Clinical Center (GNYCC) aims to engage experts in pain research and pain practice to build the infrastructure required to support the objectives of the Early Phase Pain Investigation Clinical Network (EPPIC-Net). The GNYCC will provide expertise and resources to perform phase 2 clinical trials to test the efficacy of novel pain treatments, as well as phenotyping and biomarker studies that will enable customized treatments. The consortium comprises four major academic centers in New York City, one of the most diverse cities in the United States and the nation’s largest metropolitan area. We will 1) build infrastructure to rapidly access clinical trial resources and a network of investigators and clinical leaders, 2) develop a plan for swift evaluation and launch of proposed studies, and 3) optimize patient retention and monitor sites to ensure protocol adherence, data quality, and efficiency.

The objective of the Early Phase Pain Investigation Clinical Network (EPPIC-Net) and EPPIC- Net initiatives is to rapidly and efficiently translate advances in the neurobiology of pain into treatments for people with chronic and acute pain, conditions associated with a significant burden to both patients and society. The Clinical Coordinating Center (CCC) for EPPIC-Net will promote and facilitate, from initial conception through final analysis, clinical trials in adult and pediatric populations with acute or chronic pain by providing efficient methodological, organizational, and logistical support. The EPPIC-Net-CCC will adopt and establish processes aimed at dramatically increasing the efficiency of multicenter clinical trials, improving the overall quality of clinical trials, promoting patient recruitment and retention as well as increasing the number of clinical investigators and research staff well trained and passionate about leading and conducting multicenter clinical trials.

The Helping to End Addiction Long-term? (HEAL) Initiative’s Early Phase Pain Investigation Clinical Network (EPPIC-Net) is a unique opportunity to impact the management of pain, through expeditious discovery and validation of biomarkers and analgesic therapies, and in-depth phenotyping. The University of Washington’s (UW) Division of Pain Medicine (UW Pain; “hub”) includes four core clinical sites. Committed spokes include specialty care clinics, primary care clinics, external academic medical centers, and health systems. To achieve the goals of the HEAL Initiative’s EPPIC-Net, the study group will (1) establish UW EPPIC-Net hub and spokes infrastructure, provide scientific leadership and administrative oversight, and apply expertise in design and conduct of high-quality multidisciplinary Phase 2 clinical trials and biomarker validation studies; (2) develop policies and procedures for rapid design, initiation, recruitment, conduct, and closure of high-quality multidisciplinary Phase 2 clinical trials and biomarker validation studies for specific pain conditions at UW Pain EPPIC-Net hub and spokes; and (3) establish mechanisms for communication, education and training, and performance assessment of the UW-EPPIC-Net hub and spokes, to assure efficient and timely utilization of resources to most effectively recruit research participants into EPPIC-Net.