Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
3U44NS115111-03S1
High-Resolution, Spinal Cord Stimulation for Non-Opioid Treatment of Neuropathic Pain Preclinical and Translational Research in Pain Management NINDS MICRO-LEADS, INC. MCLAUGHLIN, BRYAN L Somerville, MA 2021
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.
3R01DE029951-01S1
Targeting Endosomal Receptors for Treatment of Chronic Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDCR NEW YORK UNIVERSITY BUNNETT, NIGEL W New York, NY 2021
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:

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins and play important roles in inflammation and pain. GPCR signaling is fast and temporary, making it hard to measure in clinical studies of potential drugs to interfere with the signaling. This research is using selectively designed nanoparticles to stimulate or block GPCRs toward identifying new treatments for oral cancer pain. This award will use a new nanoformulation approach to understand how nanoparticles affect nerve function by i) testing the effects of continuous release of a GPCR inhibitor in an oral cancer microenvironment and ii) investigating the influence of various physicochemical characteristics of nanoparticles on nerve function in an oral cancer microenvironment.
1U19NS126038-01
Site-directed RNA editing of Nav1.7 as a novel analgesic Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS MARINE BIOLOGICAL LABORATORY, WOODS HOLE ROSENTHAL, JOSHUA J C (contact); DIB-HAJJ, SULAYMAN D; DUSSOR, GREGORY O; EISENBERG, ELI New Haven, CT 2021
NOFO Title: HEAL Initiative: Team Research for Initial Translational Efforts in Non-addictive Analgesic Therapeutics Development (U19 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-21-015
Summary:

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.
1R34NS126030-01
Profiling the human gut microbiome for potential analgesic bacterial therapies Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS HOLOBIOME, INC. STRANDWITZ, PHILIP PETER (contact); GILBERT, JACK ANTHONY Cambridge, MA 2021
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.
1R34NS126032-01
Stem cell-loaded microgels to treat discogenic low back pain Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS CEDARS-SINAI MEDICAL CENTER SHEYN, DMITRIY Los Angeles, CA 2021
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:

Pain caused by the degeneration of discs between vertebrae in the spine makes up a significant proportion of all chronic low back pain conditions. Although opioids are prescribed as treatments for this chronic condition, they often do not provide effective pain management, and currently there are no treatments that target the underlying disc disease. Notochordal cells mature into the cells that make up discs between vertebrae. Preliminary studies have shown that notochordal cells can be made from induced pluripotent stem cells, offering a potential replacement for diseased cells between discs. This study aims to develop a novel treatment for painful disc degeneration using a microgel/microtissue embedded with human notochordal cells made in the lab from induced pluripotent stem cells.
1UG3NS127251-01A1
Development of Pathology-Activated Drugs for Treatment of Neuropathic Pain Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF TX MD ANDERSON CAN CTR GRACE, PETER M (contact); ABELL, ANDREW Houston, TX 2022
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:

The medication monomethyl fumarate, approved for treating multiple sclerosis, has pain-relieving properties, but it also has side effects that affect the digestive tract and decrease levels of white blood cells, a problem known as leukopenia. This project will limit the availability of monomethyl fumarate to areas in the central nervous system associated with pain. Targeting the delivery of this drug to pain-related regions may improve its safety profile for treating neuropathic pain.
1R21NS130409-01
Novel Genetically Encoded Inhibitors to Probe Functional Logic of Cav-Beta Molecular Diversity Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS COLUMBIA UNIVERSITY HEALTH SCIENCES COLECRAFT, HENRY M New York, NY 2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

High-voltage-gated calcium channels convert electrical signals into physiological responses. After a nerve injury, levels of these channels go down in some neurons in the dorsal root ganglia that communicates pain signals to and from the brain. This decline results in reduced flow of calcium that may underlie pain. This project will develop novel approaches to block these calcium channels p to further study their roles in controlling pain.
1UG3NS127258-01A1
A First-in-Class, Mechanism-Guided, Cell-Based Therapy for Complex Regional Pain Syndrome Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS CLEVELAND CLINIC LERNER COM-CWRU CHENG, JIANGUO Cleveland, OH 2022
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:

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.
1R21NS130417-01
The Role of Lysosomal Mechano-Sensitive Ion Channel in Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS INDIANA UNIVERSITY PURDUE AT INDIANAPOLIS TAN, ZHIYONG Indianapolis, IN 2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Chronic pain severely reduces the quality of life and ability to work for millions of Americans. Because misuse of opioids for chronic pain treatment contributes to opioid addiction and opioid overdose, there is an urgent need to study novel non-opioid mechanisms, targets, and treatment strategies for chronic pain. Many ion channels control the flow of electrical signals in peripheral sensory neurons and are thus key targets for understanding and treating chronic pain. This project will conduct detailed studies to identify major ion channel-related molecular activities, targets, and treatment strategies for chronic pain. In particular, this research will explore the role of a specific ion channel (lysosomal mechanosensitive ion channel, orTmem63A) in neuropathic pain resulting from nerve injury.
1UC2AR082195-01
Comprehensive Functional Phenotyping of Trigeminal Neurons Innervating Temporomandibular Joint (TMJ) Tissues in Male, Female and Aged Mice, Primates, and Humans With and Without TMJ Disorders (TMJD) Preclinical and Translational Research in Pain Management Restoring Joint Health and Function to Reduce Pain (RE-JOIN) NIAMS UNIVERSITY OF TEXAS HLTH SCIENCE CENTER AKOPIAN, ARMEN N; BOADA, MARIO DANILO; ERNBERG, MALIN; MACPHERSON, LINDSEY J San Antonio, TX 2022
NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Scientists do not know the details of how the nervous system interacts with the temporomandibular joint (TMJ) that connects the lower jaw with the skull. This project aims to comprehensively explain the functions, types, neuroanatomical distributions, and adaptability (plasticity) of specific nerve cells in the brain (trigeminal neurons) that connect with the TMJ. The research will analyze nerve-TMJ connections associated with chewing muscles and other structures that form the TMJ such as cartilage and ligaments. The project will analyze samples from both sexes of aged mice, primates, and humans with and without painful TMJ disorders. This research aims to uncover potential treatment and prevention targets for managing TMJ pain.
1R21DA057500-01
G Alpha Z Subunit as a Potential Therapeutic Target to Modulate Mu Opioid Receptor Pharmacology Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDA UNIVERSITY OF ROCHESTER BIDLACK, JEAN M Rochester, NY 2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Opioids affect the body by attaching to certain types of receptors that attach to G-proteins (particularly, a subtype called G-alpha). Opioids vary in their ability to provide pain relief as well as in their ability to require more drug to provide a response, known as tolerance. This project will explore the potential of various G-alpha subunits to increase or decrease opioid receptor signaling. The research findings will lay the groundwork for tailoring G-alpha related opioid effects to provide more pain relief while being less addictive.
1UC2AR082196-01
Innervation of the Knee and TMJ  Preclinical and Translational Research in Pain Management Restoring Joint Health and Function to Reduce Pain (RE-JOIN) NIAMS UNIVERSITY OF FLORIDA ALLEN, KYLE D (contact); ALMARZA, ALEJANDRO JOSE; CAUDLE, ROBERT M Gainesville, FL 2022
NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

A complex network of different nerve cell subtypes connects to joints in different ways throughout body regions, such as the knee and the temporomandibular joint (TMJ) that connects the lower jaw and skull. This project aims to identify disease-specific pain symptoms using clinically relevant rat models of TMJ and knee osteoarthritis – and compare findings with disease-specific pain symptoms in human patients with the same conditions. This research may lead to a better understanding of how different nerve cell subtypes contribute to joint pain as well as how these nerve cell subtypes change with age and disease.
1R21TR004333-01
Discovery of Novel Openers of the Understudied Human Drug Target Kir6.1 Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCATS NEW YORK UNIVERSITY SCHOOL OF MEDICINE CARDOZO, TIMOTHY J New York, NY 2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

Routine treatment of pain with prescription opioid medications may evolve into opioid use disorder, addiction, and potentially overdose. New, non-opioid molecular targets for pain are needed as a key element of responding to the opioid and overdose crisis. Ion channels are molecular gateways that convert electrical signals into physiological responses, and many have been implicated in transmitting pain signals. The ion channel Kir6.1/KCNJ8 has been linked to the control of postoperative and cancer pain. Studies in animal models show that low levels of this ion channel are evident after an injury. This research will identify compounds that can open the Kir6.1/KCNJ8 channel as potential treatment strategy for pain.
1UC2AR082197-01
Neural Architecture of the Murine and Human Temporomandibular Joint Preclinical and Translational Research in Pain Management Restoring Joint Health and Function to Reduce Pain (RE-JOIN) NIAMS DUKE UNIVERSITY DONNELLY, CHRISTOPHER RYAN; CAI, DAWEN; EMRICK, JOSHUA JAMES Durham, NC 2022
NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Temporomandibular joint (TMJ) disorders are the most common form of chronic pain in the face and mouth area (orofacial pain), but relatively little is known about the biological causes of these conditions. This project will define the properties of sensory neurons that connect to tissues that make up the TMJ which connects the lower jaw and skull. This research aims to lay groundwork for development of new therapeutic approaches to treat these painful conditions.
1R61NS127285-01
Development of Therapeutic Antibodies to Target Sodium Channels Involved in Pain Signaling Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS University of California, Davis YAROV-YAROVOY, VLADIMIR M (contact); TRIMMER, JAMES S Davis, CA 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Voltage-gated sodium channels such as Nav1.7, Nav1.8, and Nav1.9 transmit pain signals in nerve fibers and are molecular targets for pain therapy. While Nav channels have been validated as pharmacological targets for the treatment of pain, available therapies are limited due to incomplete efficacy and significant side effects. Taking advantage of recent advances in structural biology and computational-based protein design, this project aims to develop antibodies to attach to Nav channels and freeze them in an inactive state. These antibodies can then be further developed as novel treatments for chronic pain.
1UC2AR082200-01
Neuronal Anatomy, Connectivity, and Phenotypic Innervation of the Knee Joint Preclinical and Translational Research in Pain Management Restoring Joint Health and Function to Reduce Pain (RE-JOIN) NIAMS BAYLOR COLLEGE OF MEDICINE LEE, BRENDAN (contact); ARENKIEL, BENJAMIN R; RAY, RUSSELL S; WYTHE, JOSHUA D Houston, TX 2022
NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Pain caused by degenerative joint diseases such as osteoarthritis (OA) is a major public health challenge that significantly affects quality of life for millions of Americans. There are no therapies available that offer pain relief and reverse the course of OA.  This project will use state-of-the-art technologies to create a neuronal connectivity and molecular map of the mouse knee joint, which will help identify molecular signatures that can be targeted for therapy. The research will include animals of different ages and of both sexes and test joint effects after exercise, in animals with OA, and after gene therapy that delivers an experimental OA medication directly to the joint.
1R61NS127286-01
Developing GPR37 Activators as Non-Opioid Pain Therapeutics Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS University of Texas Med BR LA, JUN-HO (contact); ALLEN, JOHN A; ZHOU, JIA Galveston, TX 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Chronic pain from tissue injury often stems from long-term changes in spinal cord circuits that change nerve sensation. Reversing these changes may provide better pain therapeutics. Previous work in animal models showed that activating G protein-coupled receptor 37 (GPR37) dampens nerve signal intensity after long-term stimulation and alleviates pain behavioral responses. This project aims to validate GPR37 in the spinal cord as a useful target for new treatments for neuropathic pain. The work will facilitate screening and identification of new molecules that activate GPR37, which can then be tested for efficacy and safety in further research in animal models of pain.
1UC2AR082186-01
Mapping the Joint-Nerve Interactome of the Knee Preclinical and Translational Research in Pain Management Restoring Joint Health and Function to Reduce Pain (RE-JOIN) NIAMS RUSH UNIVERSITY MEDICAL CENTER MALFAIT, ANNE-MARIE; LOTZ, MARTIN K; MILLER, RICHARD J Chicago, IL 2022
NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

This project will use a variety of technologies to create a comprehensive, 3D map of how sensory neurons activate knee joints in both mice and humans. The research will use imaging techniques and molecular approaches that measure gene expression. The findings will help create a comprehensive gene expression profile map of individual cells in the nerve fibers leading to the knee, as well as describe how nerve cells and joint cells interact at the most fundamental level. This research will generate a rich anatomical and molecular resource to understand the molecular basis of joint pain and guide the development of novel pain-relieving strategies.
1R61NS127287-01
Initial Development of AEG-1 Inactivation as a Possible Strategy for Pain Treatment Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS Virginia Commonwealth University DAMAJ, M IMAD (contact); SARKAR, DEVANAND Richmond, Virginia 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

There is a continued need to discover and validate new targets for potential therapeutic strategies for effective and safe treatment of pain. This project focuses on the protein metadherin, also known as astrocyte elevated gene-1 protein (AEG-1), as a possible new target for pain treatment. Preliminary studies have shown that mice genetically engineered to lack metadherin had significantly lower inflammation and chronic pain-related behaviors. This project aims to further validate AEG-1 as a pain target and test whether reducing levels in white blood cells called macrophages might work as a therapeutic strategy to reduce chronic inflammatory and/or neuropathic pain using an innovative nanoparticle approach to target specific cells.
1U19NS130607-01
INTERCEPT: Integrated Research Center for Human Pain Tissues Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS WASHINGTON UNIVERSITY GEREAU, ROBERT W Saint Louis, MO 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will use a variety of state-of-the-art technologies to generate a comprehensive  gene expression map of human peripheral nerves. The research will enhance understanding about genes involved in various painful conditions associated with nerve damage (neuropathies) resulting from injury or disease. This research will analyze DNA sequences of individual neuronal and non-neuronal cells in human nerve cells (from individuals with and without pain located outside the spinal cord that are involved in pain signal transmission. The findings, together with other imaging and computational approaches, will be used to generate a spatial atlas of the human dorsal root ganglia – a key hub for pain communication between the brain and spinal cord.
1R61NS126026-01A1
Antagonists of CRMP2 Phosphorylation for Chemotherapy-Induced Peripheral Neuropathy Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF ARIZONA KHANNA, RAJESH Tucson, Arizona 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

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.
1U19NS130608-01
Human Nociceptor and Spinal Cord Molecular Signature Center Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TEXAS DALLAS PRICE, THEODORE J (contact); CURATOLO, MICHELE ; DOUGHERTY, PATRICK M Richardson, TX 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

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.
1R61NS126029-01A1
Inhibiting RIPK1 with Necrostatin-1 for Safe and Effective Pain Treatment Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS Massachusetts General Hospital SHEN, SHIQIAN (contact); HOULE, TIMOTHY T; WANG, CHANGNING ; ZHANG, CAN MARTIN Boston, MA 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Recent studies have reported that neuropathic pain involves changes in the central nervous system that are linked to necroptosis (programmed necrotic cell death) and release of cellular components that create neuroinflammation. Necroptosis is a type of necrotic cell death affected by the protein receptor-interacting serine/threonine-protein kinase 1 (RIPK1 or RIP1). Preliminary studies also indicate that pain increases levels of RIPK1 in key brain regions implicated in pain processing. This project aims to further validate RIPK1 as a target for neuropathic pain using a newly developed positron emission tomography imaging approach. The work will pave the way for new brain-penetrant RIPK1 inhibitors as a safe, effective, and nonaddictive treatment approach for neuropathic pain.
1U19NS130617-01
Harvard PRECISION Human Pain Center Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS BRIGHAM AND WOMEN'S HOSPITAL RENTHAL, WILLIAM RUSSELL (contact); WOOLF, CLIFFORD J Boston, MA 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will use state-of-the-art technologies to analyze individual cells to characterize how human pain receptors communicate pain between the human dorsal root ganglia and the brain – including how the signals vary across diverse populations. This research will generate useful, high-quality human data about pain for further analysis and re-use by other scientific teams, toward identifying and prioritizing novel therapeutic targets for pain.
1RM1NS128775-01
Defining Mechanisms of Pain Relief Associated with Dorsal Root Ganglion and Spinal Cord Stimulation Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NINDS University of Pittsburgh KOERBER, H RICHARD (contact); LEMPKA, SCOTT F; WEBER, DOUGLAS J Pittsburgh, PA 2022
NOFO Title: HEAL Initiative: Interdisciplinary Teams to Elucidate the Mechanisms of Device-Based Pain Relief (RM1 Clinical Trial Optional)
NOFO Number: NS22-016
Summary:

Chronic pain is a debilitating condition for which there is a pressing need for safe, effective treatments. Neurostimulation therapies that target nerve structures such as the dorsal root ganglion (DRG) and the spinal cord, have shown promising results for treating chronic pain, but researchers don’t know how they work. This project focuses on two prevailing models used to explain the therapeutic effects of neurostimulation: the gate-control model in which pain signals are blocked from reaching the brain and the T-junction filtering model in which pain signals are blocked from reaching the spinal cord. Strategies will include innovative behavioral, electrophysiological, imaging, and computational modeling techniques. The results of these studies will help explain why neurostimulation therapies work and potentially offer new treatment strategies for improved pain relief.