Funded Projects
Explore our currently funded projects. You may search with all three fields, then focus your results by applying any of the dropdown filters. After customizing your search, you may download results and even save your specific search for later.
Project # | Project Title | Research Focus Area | Research Program | Administering IC | Institution(s) | Investigator(s) | Location(s) Sort descending | Year Awarded |
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1UG3TR003148-01
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Multi-organ-on-chip device for modeling opioid reinforcement and withdrawal, and the negative affective component of pain: a therapeutic screening tool. | Preclinical and Translational Research in Pain Management | Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder | NCATS | UNIVERSITY OF CALIFORNIA LOS ANGELES | MAIDMENT, NIGEL T (contact); ASHAMMAKHI, NUREDDIN ; SEIDLITS, STEPHANIE KRISTIN; SVENDSEN, CLIVE NIELS | Los Angeles, CA | 2019 |
NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003 Summary: Researchers will develop multi-organ, microphysiological systems (MPSs) based on human induced pluripotent stem cell-derived midbrain-fated dopamine (DA)/gamma-aminobutyric acid neurons on a three-dimensional platform that incorporates microglia, blood–brain barrier (BBB), and liver metabolism. RNA sequencing and metabolomics analyses will complement the primary DA release measure to identify novel mechanisms contributing to chronic opioid-induced plasticity in DA responsiveness. The chronic pain-relevant aspect of the model will be realized by examination of aversive kappa-mediated opioid effects on DA transmission in addition to commonly abused mu opioid receptor agonists, and by incorporation of inflammatory-mediating microglia. Incorporation of BBB and liver metabolism modules into the microphysiologic system platform will permit screening of drugs. Throughput will be increased by integration of online sensors for online detection of DA and other analytes. Researchers will use a curated set of 100 chemical genomics probes. |
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1R61NS131307-01
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Preclinical Assessment of a Novel Systemic Drug Candidate for Osteoarthritic Pain | Preclinical and Translational Research in Pain Management | Development and Optimization of Non-Addictive Therapies to Treat Pain | NINDS | UNIVERSITY OF SOUTHERN CALIFORNIA | EVSEENKO, DENIS | Los Angeles, CA | 2023 |
NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092 Summary: Osteoarthritis is a degenerative joint disease marked by progressively worsening chronic joint pain that affects function and quality of life. Non-opioid, alternative medications are needed for people with this condition. Joint inflammation, damage, and pain involve signaling through the interleukin-6/glycoprotein 130 pathway. This project will test blocking this pathway in rodents with a new molecule with improved drug-like properties, toward developing an oral medication for osteoarthritis. |
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3UH3NS113661-02S1
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Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain | Preclinical and Translational Research in Pain Management | Translating Discoveries into Effective Devices to Treat Pain | NINDS | UNIVERSITY OF CALIFORNIA LOS ANGELES | BARI, AUSAF; POURATIAN, NADER | Los Angeles, CA | 2020 |
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-18-906 Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-023 Summary: 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. |
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1UH3NS113661-01
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Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain | Preclinical and Translational Research in Pain Management | Translating Discoveries into Effective Devices to Treat Pain | NINDS | UNIVERSITY OF CALIFORNIA LOS ANGELES | BARI, AUSAF (contact); POURATIAN, NADER | Los Angeles, CA | 2019 |
NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018 Summary: This study aims to address critical gaps and unmet therapeutic needs of chronic low back pain (CLBP) patients using a next-generation deep brain stimulation (DBS) device with directional steering capability to engage networks known to mediate the affective component of CLBP. Researchers will utilize patient-specific probabilistic tractography to target the subgenual cingulate cortex (SCC) to engage the major fiber pathways mediating the affective component of chronic pain. The objective is to conduct an exploratory first-in-human clinical trial of SCC DBS for treatment of medically refractory CLBP. The research team aims to: (1) assess the preliminary efficacy of DBS of SCC in treatment of medically refractory CLBP; (2) demonstrate the safety and feasibility of SCC DBS for CLBP; and (3) develop diffusion tensor imaging–based blueprints of response to SCC DBS for CLBP. |
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1UG3NS128148-01A1
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Peripherally Restricted Non-Addictive Cannabinoids for Cancer Pain | Preclinical and Translational Research in Pain Management | Development and Optimization of Non-Addictive Therapies to Treat Pain | NINDS | UNIVERSITY OF CALIFORNIA LOS ANGELES | SPIGELMAN, IGOR (contact); CAHILL, CATHERINE M; FAULL, KYM FRANCIS; SCHMIDT, BRIAN L; SPOKOYNY, ALEXANDER MICHAEL | Los Angeles, CA | 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: Oral cancer pain is debilitating and difficult to treat, in part because even the most effective available pain remedies are limited by side effects. Opioid-based pain medications have several side effects including dependence and tolerance, in which the body gets used to a medicine so that either more medicine is needed or different medicine is needed. Another side effect is hyperalgesia, in which people taking opioids become more sensitive to certain painful stimuli and may misuse the drugs and risk addiction. This project will evaluate lab-made versions of cannabinoid molecules known to block pain signals in nerve cells, but which cannot enter the brain to cause neurological side effects. The research aims to advance promising versions of the molecules to testing in human research participants. |
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1R34NS126032-01
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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. |
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1U18EB029251-01
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The Injectrode - A Truly Injectable Electrode for Dorsal Root Ganglion Stimulation to Treat Pain | Preclinical and Translational Research in Pain Management | Translating Discoveries into Effective Devices to Treat Pain | NIBIB | UNIVERSITY OF WISCONSIN-MADISON | LUDWIG, KIP A (contact); WEBER, DOUGLAS J | Madison, WI | 2019 |
NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003 Summary: 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. |
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1R61NS114954-01
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The Inflammatory Index as a Biomarker for Pain in Patients with Sickle Cell Disease | Preclinical and Translational Research in Pain Management | Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions | NINDS | MEDICAL COLLEGE OF WISCONSIN | BRANDOW, AMANDA M | Milwaukee, WI | 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 pain is the most common complication of sickle cell disease (SCD), but there is significant variability in pain expression in these patients. Currently, there is no plasma biomarker that can prognosticate which patients are likely to experience pain. The overall goal of this proposed research is to develop a biomarker that prognosticates the clinical expression of pain in SCD. Project aims are to (1) derive the inflammatory index for pain by identifying inflammatory and immune regulatory gene probe sets that will distinguish healthy controls, patients with SCD in baseline health, and patients with SCD in acute pain and (2) determine whether co-expressed genes from patients with SCD correlate with clinical pain data. Subsequent aims are to (1) determine the clinically meaningful changes of the index in patients with SCD and (2) investigate the preliminary clinical validity of the index as a prognostic biomarker for pain in patients with SCD. |
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1R21TR004701-01
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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. |
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1R21NS113335-01
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Targeting the Vgf signaling system for new chronic pain treatments | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | University of Minnesota | VULCHANOVA, LYUDMILA H | Minneapolis, MN | 2019 |
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. |
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1UG3NS127943-01
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Oral N2O Therapy in Treating Acute Vaso-Occlusive Pain in Sickle Cell Disease | Preclinical and Translational Research in Pain Management | Development and Optimization of Non-Addictive Therapies to Treat Pain | NINDS | Hillhurst Biopharmaceuticals, Inc. | GOMPERTS, EDWARD (contact); BELCHER, JOHN D; SIMONE, DONALD | Montrose, CA | 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: Inhaled nitrous oxide, N2O, is used in emergency departments in Europe to treat pain associated with sickle cell disease as well as for labor, painful fractures, and to manage serious gynecological pain. It is not a viable therapeutic option for home use for reasons such as poor dosing control, potential inhalation equipment issues, and variability in patient ventilation and lung absorption. This project seeks to optimize, characterize, and develop an oral formulation of N2O that could be used by patients at home for unpredictable and severe episodes of pain associated sickle cell disease. Once developed, the new oral formulation of N2O will be evaluated to determine whether it or an optimized version is ready for more clinical testing. |
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1U18EB029351-01
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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. |
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3R01LM010685-09S1
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BEYOND PHEWAS: RECOGNITION OF PHENOTYPE PATTERNS FOR DISCOVERY AND TRANSLATION - ADMINISTRATIVE SUPPLEMENT | Preclinical and Translational Research in Pain Management | NLM | VANDERBILT UNIVERSITY MEDICAL CENTER | Denny, Joshua C. | NASHVILLE, TN | 2018 | |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Genomic medicine offers hope for improved diagnostic methods and for more effective, patient-specific therapies. Genome-wide associated studies (GWAS) elucidate genetic markers that improve clinical understanding of risks and mechanisms for many diseases and conditions and that may ultimately guide diagnosis and therapy on a patient-specific basis. Previous phenome-wide association studies (PheWAS) established a systematic and efficient approach to identifying novel disease-variant associations and discovering pleiotropy using electronic health records (EHRs). This proposal will develop novel methods to identify associations based on patterns of phenotypes using a phenotype risk score (PheRS) methodology to systematically search for the influence of Mendelian disease variants on common disease. By doing so, it also creates a way to assess pathogenicity for rare variants and will identify patients at highest risk of having undiagnosed Mendelian disease. The project is enabled by large DNA biobanks coupled to de-identified copies of EHR. |
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1UG3NS135551-01
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Translating an MR-guided focused ultrasound system for first-in-human precision neuromodulation of pain circuits | Preclinical and Translational Research in Pain Management | Translating Discoveries into Effective Devices to Treat Pain | NINDS | VANDERBILT UNIVERSITY MEDICAL CENTER | CASKEY, CHARLES F (contact); CHEN, LI MIN | Nashville, TN | 2023 |
NOFO Title: Blueprint MedTech Translator (UG3/UH3 - Clinical Trial Optional)
NOFO Number: PAR-21-315 |
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1UG3NS116218-01
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Novel mGlu5 negative allosteric modulators as first-in-class non-addictive analgesic therapeutics | Preclinical and Translational Research in Pain Management | Development and Optimization of Non-Addictive Therapies to Treat Pain | NINDS | VANDERBILT UNIVERSITY | ROOK, JERRI MICHELLE; CONN, P JEFFREY; GEREAU, ROBERT W; LINDSLEY, CRAIG | Nashville, TN | 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: An extensive literature provides compelling evidence that selective antagonists or negative allosteric modulators (NAMs) of the metabotropic glutamate (mGlu) receptor, mGlu5, have exciting potential as a novel approach for treatment of multiple pain conditions that could provide sustained antinociceptive activity without the serious adverse effects and abuse liability associated with opioids. Researchers have developed a novel series of highly selective mGlu5 NAMs that are structurally unrelated to previous compounds, have properties for further development, and avoid the formation of toxic metabolites that were associated with previous mGlu5 NAMs. Based on existing preclinical models, as well as clinical trial data showing efficacy of an mGlu5 NAM in migraine patients, researchers anticipate that their compounds will have broad-spectrum analgesic activity in patients with a variety of chronic pain conditions. |
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3UH3NS116218-02S1
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Novel mGlu5 Negative Allosteric Modulators as First-in-Class Non-Addictive Analgesic Therapeutic | Preclinical and Translational Research in Pain Management | Development and Optimization of Non-Addictive Therapies to Treat Pain | NINDS | Vanderbilt University | ROOK, JERRI MICHELLE | Nashville, TN | 2022 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements. Parent Grant: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: Supplement: PA-20-272; Parent NOFO: NS-21-010 Summary: Negative allosteric modulators (NAMs) of the metabotropic glutamate (mGlu) receptor, mGlu5, have shown promise for treatment of multiple pain conditions without the serious adverse effects and safety concerns associated with opioids. This project will develop and test a novel series of highly selective mGlu5 NAMs that are structurally unrelated to earlier failed compounds and do not form toxic byproducts as with previous mGlu5 NAMs. A lead candidate is now being characterized in several studies to assess readiness for testing in Phase I clinical studies. |
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1U19NS126038-01
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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. |
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1UG3TR003150-01
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Human Microphysiological Model of Afferent Nociceptive Signaling | Preclinical and Translational Research in Pain Management | Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder | NCATS | TULANE UNIVERSITY OF LOUISIANA | MOORE, MICHAEL J (contact); ASHTON, RANDOLPH S; RAJARAMAN, SWAMINATHAN | New Orleans, LA | 2019 |
NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003 Summary: This project will develop a human cell-based model of the afferent pain pathway in the dorsal horn of the spinal cord. The research team’s approach utilizes novel human pluripotent stem cell (hPSC)-derived phenotypes in a model that combines 3D organoid culture with microfabricated systems on an integrated, three-dimensional (3D) microelectrode array. Researchers will establish the feasibility of a physiologically relevant, human 3D model of the afferent pain pathway that will be useful for evaluation of candidate analgesic drugs. They will then improve the physiological relevance of the system by promoting neural network maturation before demonstrating the system’s utility in modeling adverse effects of opioids and screening compounds to validate the model. Completion of the study objective will establish novel protocols for deriving dorsal horn neurons from hPSCs and create the first human microphysiological model of the spinal cord dorsal horn afferent sensory pathway. |
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1R01DE029951-01
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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 | NINDS | COLUMBIA UNIVERSITY HEALTH SCIENCES | BUNNETT, NIGEL W; SCHMIDT, BRIAN L | New York, NY | 2020 |
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: Many non-opioid drugs target G Protein-Coupled Receptors (GPCRs), a family of proteins involved in many pathophysiological processes including pain, fail during clinical trials for unknown reasons. A recent study found GPCRs not only function at the surface of nerve cells but also within a cell compartment called the endosome, where their sustained activity drives pain. This study will build upon this finding and test whether the clinical failure of drugs targeting plasma membrane GPCRs is related to their inability to target and engage endomsomal GPCRs (eGPCRs). This study will use stimulus-responsive nanoparticles (NP) to encapsulate non-opioid drugs and selectively target eGPCR dyads to investigate how eGCPRs generate and regulate sustained pain signals in neuronal subcellular compartments. This study will also validate eGCPRs as therapeutic targets for treatment of chronic inflammatory, neuropathic and cancer pain. Using NPs to deliver non-opioid drugs, individually or in combinations, directly into specific compartments in nerve cells could be a potential strategy for new pain therapies. |
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1R21NS130409-01
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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. |
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1UG3NS114947-01
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Novel HCN1-selective small molecule inhibitors for the treatment of neuropathic pain | Preclinical and Translational Research in Pain Management | Development and Optimization of Non-Addictive Therapies to Treat Pain | NINDS | WEILL MEDICAL COLL OF CORNELL UNIV | GOLDSTEIN, PETER A | New York, NY | 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: Neuropathic pain is characterized by neuronal hyperexcitability and spontaneous activity, properties associated with activity of hyperpolarization-activated, cyclic nucleotide-regulated (HCN1-4) channels, the source of the pacemaker current, Ih. Inhibition of HCN1-mediated Ih elicits marked antihyperalgesia in multiple animal models of neuropathic pain, including models for direct nerve injury and chemotherapy-induced peripheral neuropathy, and does so with little or no disruption to either normal pain processing or baseline behaviors and activities. The overall objective is to develop a peripherally restricted HCN1 inverse-agonist as a therapeutic for neuropathic pain. Researchers have generated a novel small molecule that combines an antihyperalgesic HCN1 inhibitor with a motif that controls distribution and membrane presentation and is a potential non-opioid antihyperalgesic treatment for peripheral neuropathic pain. |
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3R37DA020686-13S1
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Role for Tas2Rs in opioid addiction | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NIDA | ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI | KENNY, PAUL J. | New York, NY | 2020 |
NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008 Summary: Opioids and other addictive substances have powerful rewarding properties that drive the development of addiction. They also have aversive properties that motivate their avoidance and protect against addiction. This project will explore the role of Type 2 Taste Receptor proteins (Tas2Rs or T2Rs) in regulating the aversive properties of opioids, potentially establishing an entirely new class of receptors that can be targeted for the development of novel addiction therapeutics. |
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1R21TR004333-01
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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. |
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1RM1DE033491-01
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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. |
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1R01NS131165-01A1
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Validation of Neuropilin-1 Receptor Signaling in Nociceptive Processing | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | NEW YORK UNIVERSITY | KHANNA, RAJESH | New York, NY | 2023 |
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-034 Summary: Neuropilin 1 receptor (NRP1) is a protein receptor that is active in neurons and is hypothesized to be a key mediator of sensory neuron sensitization that can lead to pain. This project will study the cellular mechanisms by which NRP1 leads to sensitization and which cell types—sensory neurons, microglia, or both—are responsible for NRP1’s role in pain. The findings can help validate NRP1 in sensory neurons and the spinal cord as a target to treat pain following nerve injury. |