Funded Projects

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA18-591
Summary:

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.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Migraine is the most common neurological disorder. Currently available treatments fail to effectively manage migraine in most patients. Development of new therapeutics has been slow due in large part to a poor understanding of the underlying pathology of migraine. Endogenous proteases, released in the meninges by resident mast cells, have been proposed as a potential driver of migraine pain via an action on protease activated receptor type 2 (PAR2). The central hypothesis is that PAR2 expression in nociceptors that project to the meninges plays a key role in the pathogenesis of migraine pain. The aims are to: 1) use the established PAR2 development pipeline to design new PAR2 antagonists with improved drug-like properties; 2) use pharmacological tools in a novel mouse migraine model to further understand the potential role of PAR2 in migraine; and 3) use mouse genetics to study the cell type–specific role of PAR2 in migraine pain.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-042
Summary:

Chronic pain is maintained, in part, by persistent changes in sensory neurons, including a pathological increase in peptides derived from the neurosecretory protein VGF (non-acronymic). Preliminary findings show that the C-terminal VGF peptide, TLQP-62, contributes to spinal cord neuroplasticity and that TLQP-62 immunoneutralization attenuates established mechanical hypersensitivity in a traumatic nerve injury model of neuropathic pain. This project will test the hypothesis that spinal cord TLQP-62 signaling can be targeted for the development of new chronic pain treatments through immunoneutralization and/or receptor inhibition. It will pursue discovery and validation of TLQP-62-based therapeutic interventions along two parallel lines: identification of TLQP-62 receptor(s) and validation of anti-TLQP-62 antibodies as a potential biological therapeutic option for chronic neuropathic pain conditions.

NOFO Title: Development and Validation of Pain-Related Models and Endpoints to Facilitate Non-Addictive Analgesic Discovery
NOFO Number: NOT-NS-22-095
Summary:

Effective development of non-addictive therapies for pain requires animal models that reflect the human condition. Unfortunately, currently used models have limitations and have not always done a good job of predicting what will work in human patients. This project will refine a new way of measuring pain-related behaviors in mice that takes advantage of more natural mouse behavior and is less influenced by experimenter biases and artifacts. The research will verify that the promising results hold up in several different types of pain and that different classes of clinically used pain medications are effective. They will also make sure the data can be reproduced by an outside laboratory. If successful, this will support the use of this new read-out for future pain therapy development.

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:

This research seeks to develop a high-resolution spinal cord stimulation therapy for treating chronic neuropathic pain of the lower extremities, groin, and lower back. Systems that use wireless communication methods require robust strategies to prevent various forms of cyberattacks on implantable devices. The focus of this project's research will be to develop a new cybersecurity risk-reduced architecture for Bluetooth low-energy implant communication.

NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Postoperative pain is a major contributor to the current opioid epidemic. Novel objective measures capable of personalizing pain care will enhance medical precision in prevention and treatment of postoperative pain. This project seeks to discover and validate a novel biosignature of the human pain experience, based on underlying IL-1 family cytokine activity and associated brain endogenous opioid function, that is readily quantifiable and clinically translatable to prevention and treatment of postoperative pain states. Specific aims will assess whether the novel biosignature will predict 1) experimentally induced pain during an experimental nociceptive pain challenge; 2) postoperative pain states with accuracy >75%, accounting for a wide range of variance in the human pain experience; and 3) postoperative pain states in an expanded clinically enriched sample.

NOFO Title: HEAL Initiative: Translational Devices to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-016
Summary:

The research team has developed ultrasonic drug uncaging for neuroscience, in which neuromodulatory agents are uncaged from ultrasound-sensitive biocompatible and biodegradable drug-loaded nanocarriers. This project will clinically translate ultrasonic ketamine uncaging for chronic pain therapy. In the UG3 phase, the research team will scale our nanoparticle production processes to human scales and adapt them to pharmaceutical standards. In the UH3 phase, they will complete a first-in-human evaluation of the safety and efficacy of ultrasonic ketamine uncaging by quantifying how much ketamine is released relative to the ultrasound dose and assessing whether the uncaged ketamine can modulate the sensitivity and affective response to pain, in patients suffering from chronic osteoarthritic pain. This project aims to yield a novel, noninvasive, non-opioid therapy for chronic pain that maximizes the therapeutic efficacy of ketamine over its side effects, by targeting its action to a critical hub of pain processing.

NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018
Summary:

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.

NOFO Title: Blueprint MedTech Translator (UG3/UH3 - Clinical Trial Optional)
NOFO Number: PAR-21-315

NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010
Summary:

Overreliance on opioids to treat chronic pain has been a contributor to the increase in individuals experiencing opioid addiction. This project aims to develop an innovative treatment approach for chronic pain that targets the cannabinoid receptor 1 (CB1R) to block the sensation of pain. The approach seeks to identify molecules that interact with a different part of the CBR1 receptor than do endocannabinoids and the primary active component of cannabis, tetrahydrocannabinol. Molecules that bind to and activate CBR1 in this different way (at an “allosteric” site) may produce nerve signaling that might differ from the effects of cannabis and endocannabinoids. This redirection of signaling pathways could help eliminate the risk of adverse effects observed with natural cannabinoids and other CBR1-binding molecules. The goal of this project is to identify a CB1R allosteric molecule, conduct studies toward obtaining federal permission to develop it as a medication, and to test it in a Phase I clinical study.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

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.

NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-21-029
Summary:

Common chronic pain syndromes such as fibromyalgia, temporomandibular disorder, and low back pain, are significant health conditions for which safe and effective treatments are needed. Previous studies have identified the adrenergic receptor beta-3 (Adrb3) as a novel target for chronic pain, but past attempts to block this receptor have not worked. This project aims to identify and develop new molecules to attach selectively and block Adrb3 without entering the brain and spinal cord. The research will test these molecules in rodent animal models to determine their ability to block pain without significant side effects.

NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010