Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1UG3NS123958-01
Development of a CCKBR-targeting scFv as Therapy for Chronic Pain Patients Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR WESTLUND-HIGH, KARIN N (contact); ALLES, SASCHA R Albuquerque, NM 2021
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:

Cholecystokinin B receptor (CCKBR) is a molecule found in the brain that helps regulate anxiety and depression but also influences the development of tolerance to opioids. CCKBR levels are also increased in models of nerve injury-induced (neuropathic) pain. Therefore, targeting CCKBR may offer a new approach to treating neuropathic pain and the associated anxiety and depression. Researchers have developed mouse antibodies that can inactivate CCKBR. However, to be usable in humans without causing an immune response, these antibodies need to be modified to include more human sequences. This project will use a fragment of the CCKBR antibody, modify it with the addition of human antibody sequences, and then select the clones that bind most strongly and specifically to human CCKBR. These will then be tested in cell and animal models of neuropathic pain to identify the most promising candidates for further evaluation in humans.
1R61NS133704-01
Development of Adrb3 Antagonists for the Treatment of Pain Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS DUKE UNIVERSITY NACKLEY, ANDREA G (contact); JIN, CHUNYANG Durham, NC 2023
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.
1U18EB029351-01
Development of an MRgFUS system for precision-targeted neuromodulation of pain circuits with simultaneous functional MRI Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NIBIB VANDERBILT UNIVERSITY MEDICAL CENTER CASKEY, CHARLES F (contact); CHEN, LI MIN ; GRISSOM, WILLIAM A Nashville, Tennessee 2019
NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003
Summary:

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.
1U18EB029353-01
Development of a Wireless Endovascular Nerve Stimulator for Treatment of Refractory Neuropathic Pain Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NIBIB BAYLOR COLLEGE OF MEDICINE KAN, PETER TZE MAN; ROBINSON, JACOB T; SHETH, SUNIL Houston, TX 2019
NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003
Summary:

For patients with neuropathic pain refractory to therapy using small molecules, modulation of specific neural structures in the central or peripheral nervous system can provide effective alternative treatments. While current Food and Drug Administration–approved devices for dorsal root ganglion (DRG) stimulation are safe and effective, there have been an unfortunate number of adverse events associated with pulse generator infections and lead migration. The research team will develop a wireless, millimeter-sized nerve stimulator that can be delivered through the vasculature and stimulate the DRG to alleviate symptoms of neuropathic pain and the associated minimally invasive delivery method. This endovascular nerve stimulation (EVNS) system depends on development and integration of key novel technologies into an endovascular stent. The magnetoelectric transducers and electronic circuits will convert wireless power and data into stimulus patterns that can trigger neural activity in the DRG via miniature electrodes. After chronic demonstration of safety and functionality in large animal models, the team will prepare for regulatory discussions with the FDA. If successful, the EVNS will provide a technology platform for treating other neuropathic pain syndromes. 
1R61NS131188-01
Development of LPA5 Antagonists as Analgesics Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS RESEARCH TRIANGLE INSTITUTE ZHANG, YANAN (contact); LI, JUN-XU; TAO, YUAN-XIANG Research Triangle Park, NC 2023
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:

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.  
1UG3NS115718-01
Development of MRGPRX1 positive allosteric modulators as non-addictive therapies for neuropathic pain Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS JOHNS HOPKINS UNIVERSITY TSUKAMOTO, TAKASHI Baltimore, NC 2019
NOFO Title: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-010
Summary:

Although opioid-based analgesics have been proven effective in reducing the intensity of pain for many neuropathic pain conditions, their clinical utility is grossly limited due to the substantial risks involved in such therapy, including nausea, constipation, physical dependence, tolerance, and respiratory depression. Cumulative evidence suggests that human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain with limited side effects due to its restricted expression in nociceptors within the peripheral nervous system; however, direct activation of MRGPRX1 at peripheral terminals is expected to induce itch side effects, limiting the therapeutic utility of orthosteric MRGPRX1 agonists. This finding led to the exploration of positive allosteric modulators (PAMs) of MRGPRX1 to potentiate the effects of the endogenous agonists at the central terminals of sensory neurons without activating peripheral MRGPRX1. An intrathecal injection of a prototype MRGPRX1 PAM, ML382, effectively attenuated evoked, persistent, and spontaneous pain without causing itch side effects. The goal of this study is to develop a CNS-penetrant small-molecule MRGPRX1 PAM that can be given orally to treat neuropathic pain conditions.
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.
1UG3NS131304-01
Development of Positive TMEM97 Modulators for Treating Neuropathic Pain Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS NUVONURO, INC. MARTIN, STEPHAN Austin, TX 2023
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:

Neuropathic pain is a debilitating and complex medical condition for which safe and non-addictive treatment options are urgently needed. This project aims to develop new strategies for treating neuropathic pain by controlling the activity of transmembrane protein 97 (TMEM97), also known as the sigma 2 receptor, which has been shown to relieve pain in an animal model of neuropathic pain. The research aims to develop a new molecule that increases TMEM97 activity and is safe for human use, toward obtaining approval from the U.S. Food and Drug Administration for Phase I clinical testing. 
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.
1R61NS113316-01
Discovery and analytical validation of Inflammatory bio-signatures of the human pain experience Preclinical and Translational Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON PROSSIN, ALAN RODNEY Houston, TX 2019
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.
1RF1NS113881-01
Discovery and validation of a new long noncoding RNA as a novel target for neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS RBHS-NEW JERSEY MEDICAL SCHOOL TAO, YUAN-XIANG Newark, NJ 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Identification of new targets and mechanisms underlying chronic neuropathic pain is essential for the discovery of novel treatments and preventative tactics for better neuropathic pain management. A recent exploration of next-generation RNA sequencing identified a large, native, full-length long noncoding RNA (lncRNA) in mouse and human dorsal root ganglion (DRG). It was named as nerve injury-specific lncRNA (NIS-lncRNA), since its expression was found increased in injured DRGs, in response to peripheral nerve injury, but not in response to inflammation. Preliminary findings revealed that blocking the nerve injury-induced increases in DRG NIS-lncRNA levels ameliorated neuropathic pain. This project will validate NIS-lncRNA as a therapeutic target in animal models of neuropathic pain and in cell-based functional assays utilizing human DRG neurons. Completion of this proposal will advance neuropathic pain management and might provide a novel, non-opioid pain therapeutic target.
1R01NS113257-01
Discovery and validation of a novel orphan GPCR as a target for therapeutic intervention in neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS St. Louis University SALVEMINI, DANIELA St. Louis, MO 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Neuropathic pain conditions are exceedingly difficult to treat, and novel non-opioid analgesics are desperately needed. Receptomic and unbiased transcriptomic approaches recently identified the orphan G-protein coupled receptor (oGPCR), GPR160, as a major oGPCR whose transcript is significantly increased in the dorsal horn of the spinal cord (DH-SC) ipsilateral to nerve injury, in a model of traumatic nerve-injury induced neuropathic pain caused by constriction of the sciatic nerve in rats (CCI). De-orphanization of GPR160 led to the identification of cocaine- and amphetamine-regulated transcript peptide (CARTp) as a ligand which activates pathways crucial to persistent pain sensitization. This project will test the hypothesis that CARTp/GPR160 signaling in the spinal cord is essential for the development and maintenance of neuropathic pain states. It will also validate GPR160 as a non-opioid receptor target for therapeutic intervention in neuropathic pain, and characterize GPR160 coupling and downstream molecular signaling pathways underlying chronic neuropathic pain.
1R61NS113329-01
Discovery of Biomarker Signatures Prognostic for Neuropathic Pain after Acute Spinal Cord Injury Preclinical and Translational Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON HERGENROEDER, GEORGENE W Houston, TX 2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Debilitating neuropathic pain occurs in 40 percent to 70 percent of people who suffer from spinal cord injury (SCI). There are no distinguishing characteristics to identify who will develop neuropathic pain. The objective of this research is to develop a biomarker signature prognostic of SCI-induced neuropathic pain (NP). The aims of the project are to (1) identify autoantibodies in plasma samples from acute SCI patients to CNS autoantigens and determine the relationship between autoantibodies levels to the development of NP, (2) identify the autoantibody combination with maximal prognostic accuracy for the development of NP at six months after SCI, and (3) develop and optimize an assay to simultaneously measure several autoantibodies and independently validate the prognostic efficacy for NP using plasma samples collected prospectively. Establishing a panel will refine the prognostic value of these autoantibodies as biomarkers to detect who are vulnerable to NP and may be used to for development of nonaddictive pain therapeutics.
1U44NS111779-01
DISCOVERY OF NAV1.7 INHIBITORS FOR THE TREATMENT OF PAIN Preclinical and Translational Research in Pain Management NINDS SITEONE THERAPEUTICS, INC. MULCAHY, JOHN VINCENT; ODINK, DEBRA BOZEMAN, MT 2019
NOFO Title: Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development for Disorders of the Nervous System (U44 Clinical Trial Optional)
NOFO Number: PAR-18-541
Summary:

We propose to develop a safe and effective nonopioid analgesic to treat neuropathic pain that targets an isoform of the voltage-gated sodium ion channel, NaV1.7. Voltage-gated sodium channels are involved in the transmission of nociceptive signals from their site of origin in the peripheral terminals of DRG neurons to the synaptic terminals in the dorsal horn. NaV1.7 is the most abundant tetrodotoxin-sensitive sodium channel in small diameter myelinated and unmyelinated afferents, where it has been shown to modulate excitability and set the threshold for action potentials. Development of systemic NaV1.7 inhibitors has been complicated by the challenge of achieving selectivity over other NaV isoforms expressed throughout the body. We have discovered a series of potent, state-independent NaV1.7 inhibitors that exhibit >1000-fold selectivity over other human isoforms. Work conducted under this program will support advancement of a lead candidate into clinical development as a therapeutic for neuropathic pain.
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.
1R61NS113341-01
Discovery of the Biomarker Signature for Neuropathic Corneal Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS Tufts Medical Center HAMRAH, PEDRAM Boston, MA 2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Neuropathic corneal pain (NCP) causes patients to have severe discomfort and a compromised quality of life (QoL). The lack of signs observed by standard examination has resulted in misdiagnosis as dry eye disease (DED). An optical biopsy using laser in vivo confocal microscopy (IVCM) revealed that microneuromas (bulbs at the ends of severed nerves caused by buildup of molecular constituents) are present in NCP but not DED and may serve as a biomarker for NCP. The aims are to (1) use a database of more than 2,000 DED/NCP subjects and more than 500,000 IVCM images to confirm that the presence of microneuromas is an appropriate biomarker for NCP, (2) provide biological validation of microneuromas, (3) develop a validated artificial intelligence (AI) program for automated identification of microneuromas, and (4) establish the clinical utility of microneuromas observed by IVCM as a biomarker for NCP in a prospective, multicenter study.
1R21NS132565-01
Discovery of the Novel Targets for Post-Traumatic Headache Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS WASHINGTON UNIVERSITY CAO, YUQING Saint Louis, MO 2023
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: RFA-TR-22-011
Summary:

Chronic post-traumatic headache (PTH) is highly debilitating, poorly understood, and difficult to treat. This project aims to identify proteins located in the membrane of certain neurons that are critical for the development, maintenance, and/or resolution of PTH. These proteins may be targets for novel treatment approaches that are nonaddictive and have minimal side effects.
4UH3NS123964-02
Disease Modifying Analgesia with CA8 Gene Therapy Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF MIAMI SCHOOL OF MEDICINE LEVITT, ROY C Coral Gables, FL 2023
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
1UG3NS123964-01
Disease Modifying Analgesia with CA8 Gene Therapy Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF MIAMI SCHOOL OF MEDICINE LEVITT, ROY C Coral Gables, FL 2021
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:

Efforts to identify non-opioid analgesics for treatment of chronic pain have identified a protein, carbonic anhydrase-8 (CA8), in pain-sensing nerve cells in the spinal cord (dorsal root ganglion cells) whose expression regulates analgesic responses. Gene therapy delivering CA8 to dorsal root ganglion cells through clinically relevant routes of administration functions as a “local anesthetic” that induces long-lasting pain relief in animal models of chronic pain. This project will further develop CA8 gene therapy with the goal of treating chronic knee osteoarthritis pain. It will assess several gene therapy constructs to determine the doses needed, safety, efficacy, and specificity to nerve cells for each construct. It will then select the safest and most effective construct that can be administered via the least invasive route for further development. The project will include all steps necessary to identify one candidate gene therapy construct that will be suitable to begin clinical trials in patients with chronic knee osteoarthritis pain.
1RF1NS113991-01
Disrupting ion channel scaffolding to treat neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS STATE UNIVERSITY OF NEW YORK AT BUFFALO BHATTACHARJEE, ARINDAM Buffalo, NY 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Dorsal root ganglion (DRG) neuronal hyperexcitability is central to the pathology of neuropathic pain and is a target for local anesthetics, even though the efficacy of local anesthetic patches has been mixed. The coordinated movement of ion channels, especially voltage-dependent sodium channels, from intracellular pools to the sites of nerve injury has been suggested to be an underlying cause of electrogenesis and ectopic firing in neuropathic pain conditions. Recent studies identified Magi1 as a scaffold protein responsible for sodium channel targeting and membrane stabilization in DRG neurons. This project will determine whether reducing the expression Magi1 could disrupt intracellular trafficking of sodium channels in DRG neurons under neuropathic injury conditions, and could therefore serve as a potential therapeutic target for neuropathic pain.
3U19TW008163-10S1
DIVERSE DRUG LEAD COMPOUNDS FROM BACTERIAL SYMBIONTS IN PHILIPPINE MOLLUSKS Preclinical and Translational Research in Pain Management FIC UNIVERSITY OF UTAH HAYGOOD, MARGO GENEVIEVE Salt Lake City, UT 2018
NOFO Title: Limited Competition: International Cooperative Biodiversity Groups (U19)
NOFO Number: RFA-TW-13-001
Summary:

The Philippine Mollusk Symbiont International Cooperative Biodiversity Group harnesses the vast biodiversity of the Philippines to discover new drugs to treat bacterial infections, parasitic infections, pain, and other neurological conditions and cancer, all of which are serious health problems in both the Philippines and the United States. The Republic of the Philippines represents a unique nexus of exceptional biodiversity, dense human population with pressing societal needs, consequent urgent need for conservation, and government commitment to education and technology to harness national human and natural resources for a sustainable future. Mollusks are one of the most diverse groups of marine animals, and their associated bacteria represent an unexplored trove of chemical diversity. Researchers will use an increasing understanding of the interactions between mollusk symbionts and their hosts to discover the most novel and useful molecules. The project will document and describe Philippine mollusk biodiversity and support training and infrastructure that provide the foundation for conservation of Philippine biodiversity.
1RF1NS113256-01
Dnmt3a as an epigenetic target for chronic pain treatment Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TX MD ANDERSON CAN CTR PAN, ZHIZHONG Z Houston, TX 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

It is unclear what changes in the brain mediate the development of chronic pain from acute pain and how chronic pain may change responses to opioid reward for the altered liability of opioid abuse under chronic pain. Preliminary studies have found that Dnmt3a, a DNA methyltransferase that catalyzes DNA methylation for gene repression, is significantly downregulated in the brain in a time-dependent manner during the development of chronic pain and after repeated opioid treatment. This project will investigate whether Dnmt3a acts as a key protein in the brain for the development of chronic pain, and whether Dnmt3a could be a novel epigenetic target for the development of new drugs and therapeutic options for the treatment of chronic pain while decreasing abuse liability of opioids.
1RM1DE033491-01
Endosomal Mechanisms Signaling Oral Cancer Pain Preclinical and Translational Research in Pain Management Integrated Basic and Clinical Team-Based Research in Pain NIDCR NEW YORK UNIVERSITY SCHMIDT, BRIAN L (contact); BUNNETT, NIGEL W; KHANNA, RAJESH; LEONG, KAM W; YE, YI New York, NY 2023
NOFO Title: HEAL Initiative Integrated Basic and Clinical Team-based Research in Pain (RM1 Clinical Trial Optional)
NOFO Number: RFA-NS-22-069
Summary:

Human oral cancer is associated with significant chronic pain, and a comprehensive understanding of the biology and mechanisms underlying this chronic pain is critical for developing better pain management strategies. This project will determine molecular characteristics, including a specific signaling system (endosomal GPCR kinase), associated with chronic oral cancer pain, using tissue samples obtained from patients with this condition. The findings will then be used to inform studies in animal models of human oral cancer pain to enhance understanding how endosomal GPCR kinase contributes to human oral cancer pain.
1R21AT012304-01
Erythrocyte Autophagy Proteins as Potential Non-Opioid Novel Targets for Pain in Sickle Cell Disease Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCCIH UNIVERSITY OF ILLINOIS, CHICAGO RAMASAMY, JAGADEESH Chicago, IL 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:

Sickle cell disease is an inherited blood disorder affecting about 100,000 Americans and over 20 million people worldwide. It is caused by a mutation in the gene for beta-globin that results in the characteristic sickled shape of red blood cells, life-long severe pain, and shortened lifespan. Painful episodes that require hospitalization and, in many cases, opioid treatment, are a hallmark of sickle cell disease. The source of these painful episodes remains unclear, and it is also unknown why pain severity varies so much among affected individuals. This project will identify novel, non-opioid targets to reduce sickle cell-related pain and search for biomarkers to help clinicians predict which individuals are at risk for increased pain, thereby improving health outcomes for people with sickle cell disease.
1R21TR004701-01
Exploration of MBD1 as a Therapeutic Target for Chronic Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCATS UNIVERSITY OF MINNESOTA STONE, LAURA S Minneapolis, MN 2023
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: RFA-TR-22-011
Summary:

Chronic pain results in long-term changes throughout the central nervous system. These include abnormal structure and function of the frontal cortex region of the brain, which relays pain messages and also the common pain-related conditions depression, anxiety, and cognitive impairment. Peripheral nerve injury results in widespread and long-lasting changes to DNA in the frontal cortex. DNA methylation, in which chemical tags are attached to DNA, is one way the body controls the activity of genes over time. This control occurs via proteins that recognize tagged DNA, and some of these proteins do not work properly in the frontal cortex many months after nerve injury. These changes occur after nerve injury and are linked to mechanical sensitivity. This project will determine this DNA-binding protein is a good target for finding new medications for chronic pain.