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) | Year Awarded |
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3U24TR001608-04S1
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TIN Supplement | Clinical Research in Pain Management | Pain Management Effectiveness Research Network (ERN) | NCATS | Duke University | Benjamin, Daniel K. | Durham, NC | 2019 |
NOFO Title: CTSA Network - Trial Innovation Centers (TICs) (U24)
NOFO Number: RFA-TR-15-002 |
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1R43CA233371-01A1
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Inhibiting soluble epoxide hydrolase as a treatment for chemotherapy inducedperipheral neuropathic pain | Cross-Cutting Research | Small Business Programs | NCI | EICOSIS, LLC | BUCKPITT, ALAN R | Davis, CA | 2019 |
NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574 Summary: Investigating the broader efficacy of sEH inhibition and specifically our IND candidate, EC5026, has indicated that it is efficacious against chemotherapy induced peripheral neuropathy (CIPN). This painful neuropathy develops from chemotherapy treatment, is notoriously difficult to treat, and can lead to discontinuation of life-prolonging cancer treatments. Thus, new therapeutic approaches are urgently needed. The research team will investigate if EC5026 has potential drug-drug interaction with approved chemotherapeutics or alters immune cells function, and assess the effects of sEHI on the lipid metabolome and probe for changes in endoplasmic reticulum stress and axonal outgrowth in neurons. The team proposes to more fully characterize the analgesic potential of our compound and investigate on and off target actions in CIPN models and model systems relevant to cancer therapy. |
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1UG3AG067593-01
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Non-pharmacological Options in postoperative Hospital-based And Rehabilitation pain Management (NOHARM) pragmatic clinical trial | Clinical Research in Pain Management | Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) | NIA | MAYO CLINIC ROCHESTER | CHEVILLE, ANDREA LYNNE (contact); TILBURT, JON C | Rochester, MN | 2019 |
NOFO Title: HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM)(UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-AT-19-004 Summary: Prescriptions for narcotic pain relief after surgery result in unintended prolonged opioid use for hundreds of thousands of Americans. Nonpharmacological pain care is effective and recommended by guidelines for perioperative pain while offering a more favorable risk-benefit ratio. However, nonpharmacological pain care is rarely used as first or second-line therapy after surgery. Patient and clinician decision support interventions are effective in encouraging patient-centered and guideline-concordant care, but these strategies have not been tested pragmatically as a bundle in everyday postoperative pain care. The NOHARM trial will first confirm the feasibility of patient-facing and clinician-facing decision support components of an EHR-embedded evidence-based bundle. The investigators will test the bundle in a stepped-wedge cluster randomized trial. They will test a sustainable system strategy that could change the paradigm of perioperative pain management toward nonpharmacological options in a manner that preserves patient function, honors patient values, and maintains availability of opioids as a last resort. |
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1UG3AR077360-01
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A sequenced-strategy for improving outcomes in patients with knee osteoarthritis pain | Clinical Research in Pain Management | Pain Management Effectiveness Research Network (ERN) | NIAMS | JOHNS HOPKINS UNIVERSITY | COHEN, STEVEN P (contact); CAMPBELL, CLAUDIA MICHELLE; CASTILLO, RENAN C | Baltimore, MD | 2019 |
NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-19-021 Summary: The goal of this proposal is to conduct a randomized controlled trial to evaluate the comparative effectiveness of conservative behavioral and nonopioid pharmacological treatments (Phase I) and, among nonresponders, the benefits of nonsurgical procedural interventions (Phase II). Aim 1 will evaluate the effectiveness of individual and combined online cognitive behavioral therapy (painTRAINER) and pharmacologic treatment (duloxetine) in improving pain and function for knee osteoarthritis (KOA) patients compared with standard of care. Aim 2 will determine if genicular nerve radiofrequency ablation or intra-articular injection of hyaluronic acid and steroid is more effective in improving outcomes than local anesthetic nerve block or standard of care and help establish the role of these interventional treatments in the overall management of pain in KOA patients. Aim 3 will test whether clinical and psychosocial phenotypes predict short- and long-term treatment response. |
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5R01NS097880-02
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Regulation of neuropathic pain by exercise: effects on nociceptor plasticity and inflammation | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | DREXEL UNIVERSITY | DETLOFF, MEGAN R | Philadelphia, PA | 2018 |
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073 Summary: Spinal cord injury (SCI) impairs sensory transmission leading to chronic, debilitating neuropathic pain. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. In the lab, we have shown the timing of exercise is critical to meaningful sensory recovery. Early administration of a sustained locomotor exercise program in spinal cord–injured rats prevents the development of neuropathic pain, while delaying similar locomotor training until pain was established was ineffective at ameliorating it. The time elapsed since the injury occurred also indicates the degree of inflammation in the dorsal horn. We have previously shown that chronic SCI and the development of neuropathic pain correspond with robust increases in microglial activation and the levels of pro-inflammatory cytokines. This proposal seeks to lengthen the therapeutic window where rehabilitative exercise can successfully suppress neuropathic pain by pharmacologically reducing inflammation in dorsal root ganglia. |
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1U01DK123787-01
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University of Illinois at Chicago Hemodialysis Opioid Prescription Effort (HOPE) Clinical Center | Clinical Research in Pain Management | Integrated Approach to Pain and Opioid Use in Hemodialysis Patients | NIDDK | UNIVERSITY OF ILLINOIS AT CHICAGO | FISCHER, MICHAEL J (contact); DOORENBOS, ARDITH Z | Chicago, IL | 2019 |
NOFO Title: HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium - Clinical Centers (U01 Clinical Trial Required)
NOFO Number: RFA-DK-18-030 Summary: This study will evaluate novel strategies to reduce opioid use and pain in patients with end-stage renal disease receiving chronic hemodialysis (HD). Specifically, the study will examine the effect of nonpharmacologic (Acceptance and Commitment Therapy [ACT] and acupuncture) and pharmacologic (buprenorphine) interventions in HD patients who are receiving chronic opioid medications due to chronic pain and/or high pain interference. The study will enroll 720 HD patients across U.S. Hemodialysis Opioid Prescription Effort Consortium Clinical Centers to (1) determine the effectiveness of ACT and acupuncture compared with the control condition in reducing opioid dose and improving pain among HD patients; (2) identify the best adaptive intervention sequence for improved outcomes; (3) explore age, sex, and comorbidities as potential moderators of the response to the intervention; and (4) describe facilitators and barriers to the implementation of the intervention using in-depth, semi-structured individual interviews with intervention participants and providers. |
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1R61NS113341-01
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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. |
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1U24NS115679-01
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MACC/EPICC-Net as a Hub for the HEAL Initiative EPICC-Net | Clinical Research in Pain Management | Early Phase Pain Investigation Clinical Network (EPPIC-Net) | NINDS | MEDICAL COLLEGE OF WISCONSIN | HERNANDEZ-MEIER, JENNIFER LYNN (contact); AUFDERHEIDE, TOM PAUL | Madison, WI | 2019 |
NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-036 |
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3R01NS045594-14S1
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Study of Activity Dependent Sympathetic Sprouting | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | UNIVERSITY OF CINCINNATI | JUN-MING, Zhang | Cincinnati, OH | 2019 |
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073 Summary: Many chronic pain conditions are dependent upon activity of the sympathetic nervous system. Sympathetic blockade is used clinically in chronic pain conditions, but the clinical and preclinical evidence for this practice is incomplete. We propose that certain pathological pain conditions require intact sympathetic innervation of the sensory nervous system at the level of the dorsal root ganglion (DRG) and that release of sympathetic transmitters enhances local inflammation and leads to pain. Our preliminary data show large, rapid, and long-lasting reduction of pain behaviors and inflammatory responses following a"microsympathectomy" (mSYMPX) in both neuropathic and inflammatory pain models. Our aims are to: 1) characterize the effects of mSYMPX on pain and on local inflammation in the DRG; 2) explore the molecular mechanisms for sympathetic regulation of inflammatory responses in the DRG; and 3) assess the functional role of sympathetic transmitters in the sympathetically mediated inflammatory responses in the DRG. |
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1R44AR074820-01A1
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A phenotypic screen for osteoarthritic pain therapeutics using all-optical electrophysiology | Cross-Cutting Research | Small Business Programs | NIAMS | QUELL TX, INC. | LIU, PIN; MCMANUS, OWEN B | Cambridge, MA | 2019 |
NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574 Summary: Quell Therapeutics uses the Optopatch platform for making all-optical electrophysiology measurements in neurons at a throughput sufficient for phenotypic screening. Using engineered optogenetic proteins, blue and red light can be used to stimulate and record neuronal activity, respectively. Custom microscopes enable electrophysiology recordings from 100’s of individual neurons in parallel with high sensitivity and temporal resolution, a capability currently not available with any other platform screening technology. Here, researchers combine the Optopatch platform with an in vitro model of chronic pain, where dorsal root ganglion (DRG) sensory neurons are bathed in a mixture of inflammatory mediators found in the joints of osteoarthritis patients. The neurons treated with the inflammatory mixture become hyperexcitable, mimicking the anticipated cellular pain response. Investigators calculate the functional phenotype of arthritis pain, which captures the difference in action potential shape and firing rate in response to diverse stimuli. The team will screen for small molecule compounds that reverse the pain phenotype while minimizing perturbation of neuronal behavior orthogonal to the pain phenotype, the in vitro “side effects.” The highest ranking compounds will be chemically optimized and their pharmacokinetic, drug metabolism, and in vivo efficacy will be characterized. The goal is to advance therapeutic discovery for pain, which may ultimately help relieve the US opioid crisis. |
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1U24NS113784-01
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University of Rochester Hub and Spokes for the EPPIC Network - Specialized Clinical Center | Clinical Research in Pain Management | Early Phase Pain Investigation Clinical Network (EPPIC-Net) | NINDS | UNIVERSITY OF ROCHESTER | MARKMAN, JOHN DOUGLAS (contact); GEWANDTER, JENNIFER | Rochester, NY | 2019 |
NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trials Not Allowed)
NOFO Number: RFA-NS-19-025 Summary: The NIH’s HEAL Initiative aims to support collaboration between clinical research experts in academia and industry to accelerate the development of highly efficacious, nonaddictive analgesics for well-defined chronic pain syndromes. The University of Rochester (UR), and its leadership for the UR Hub and Spokes within Early Phase Pain Investigation Clinical Network (EPPIC-Net), will recruit subjects with a broad range of pain conditions, with a focus on leveraging clinical trial infrastructure to support patient recruitment and retention, timely and accurate data entry, and regulatory documentation, as well as recruit additional Spoke sites through a national network of analgesic researchers. |
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5R01NS102432-02
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AIBP and regulation of neuropathic pain | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | Univ. of Calif., U.C. San Diego | Miller, Yury | La Jolla, CA | 2018 |
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073 Summary: Persistent pain states arising from inflammatory conditions, such as in arthritis, diabetes, HIV, and chemotherapy, exhibit a common feature in the release of damage-associated molecular pattern molecules, which can activate toll-like receptor-4 (TLR4). Previous studies suggest that TLR4 is critical in mediating the transition from acute to persistent pain. TLR4 as well as other inflammatory receptors localize to lipid raft microdomains on the plasma membrane. We have found that the secreted apoA-I binding protein (AIBP) accelerates cholesterol removal, disrupts lipid rafts, prevents TLR4 dimerization, and inhibits microglia inflammatory responses. We propose that AIBP targets cholesterol removal to lipid rafts harboring activated TLR4. The aims of this proposal are to: 1) determine whether AIBP targets lipid rafts harboring activated TLR4; 2) test whether AIBP reduces glial activation and neuroinflammation in mouse models of neuropathic pain; and 3) identify the origin and function of endogenous AIBP in the spinal cord. |
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1R01DK123138-01
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Validation of peripheral CGRP signaling as a target for the treatment of pain in chronic pancreatitis | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NIDDK | JOHNS HOPKINS UNIVERSITY | PASRICHA, PANKAJ J | Baltimore, MD | 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: Chronic pancreatitis (CP) and the debilitating pain associated with it remains a common and challenging clinical syndrome that is difficult to treat effectively. Using rodent models of CP, preliminary studies have found that nerve growth factor (NGF) and transforming growth factor beta (TGFb) appear to be acting by the common effector, calcitonin-gene related peptide (CGRP), to induce pain in CP. CGRP is known to mediate pain as a neurotransmitter in the central nervous system, specifically as a potent vasodilator involved in migraine. This project will test the hypothesis that peripheral CGRP is a major mediator of peripheral nociceptive sensitization in CP, and that peripherally restricted anti-CGRP treatment could provide an efficient and sufficient approach for the treatment of pain in pancreatitis |
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2R44DA045410-02
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Peripherally-Restricted Long-Acting Somatostatin Receptor 4 (LA-SSTR4) Agonists for Pain | Cross-Cutting Research | Small Business Programs | NIDA | PEPTIDE LOGIC, LLC | RIVIERE, PIERRE | San Diego, CA | 2019 |
NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574 Summary: The proposed SBIR Phase II program seeks to select a first-in-class, peripherally-restricted, and long-acting somatostatin receptor 4 (LA-SSTR4) agonist clinical candidate for development as a novel non-addictive analgesic able to replace opioids for the treatment of moderate-to-severe chronic pain. The program is based on strong scientific evidence showing that activation of peripheral SSTR4 produces broad spectrum analgesic activity and pursues a unique therapeutic strategy. Unlike opioids, SSTR4 agonists do not induce constipation, respiratory depression, dependence, addiction, or abuse. Finally, unlike SSTR2 and SSTR5, SSTR4 expression in the pituitary and pancreas is very low, supporting that selective SSTR4 agonists are unlikely to perturb peripheral endocrine functions. The preceding SBIR Phase I program has already established the feasibility of conjugating a short-acting, potent, and selective peptide SSTR4 agonist to the antibody carrier. The resulting LA-SSTR4 agonist lead series has high agonist potency and selectivity for SSTR4 and has demonstrated antinociceptive activity in an animal pain model. The proposed SBIR Phase II program seeks to: optimize the existing lead series and select a clinical candidate for development, validate and prioritize the indication(s) for clinical development using disease-relevant mouse pain models, and characterize the pharmacokinetics and safety/toxicology profile of the clinical candidate in rat and non-human primates to help design subsequent investigational new drug (IND)-enabling studies. |
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1UH3NS115631-01
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Multisite adaptive brain stimulation for multidimensional treatment of refractory chronic pain | Preclinical and Translational Research in Pain Management | Translating Discoveries into Effective Devices to Treat Pain | NINDS | UNIVERSITY OF CALIFORNIA, SAN FRANCISCO | SHIRVALKAR, PRASAD | San Francisco, CA | 2019 |
NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018 Summary: The research team will develop stimulation control algorithms to treat chronic pain using a novel device that allows longitudinal intracranial signal recording in an ambulatory setting. Subjects with refractory chronic pain syndromes will undergo bilateral surgical implant of temporary electrodes in the thalamus, anterior cingulate, prefrontal cortex, insula, and amygdala to identify candidate biomarkers of pain and optimal stimulation parameters. Six patients will proceed to chronic implantation of “optimal” brain regions for long-term recording and stimulation. The team will first validate biomarkers of low- and high-pain states to define neural signals for pain prediction in individuals. They will then use these pain biomarkers to develop personalized closed-loop algorithms for deep-brain stimulation (DBS) and test the feasibility of closed-loop DBS for chronic pain in weekly blocks. Researchers will assess the efficacy of closed-loop DBS algorithms against traditional open-loop DBS or sham in a double-blinded cross-over trial and measure mechanisms of DBS tolerance. |
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1RF1NS113881-01
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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. |
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1R44AR076885-01
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Enhancing Physical Therapy: Noninvasive Brain Stimulation System for Treating Carpal Tunnel Syndrome | Cross-Cutting Research | Small Business Programs | NIAMS | HIGHLAND INSTRUMENTS, INC. | WAGNER, TIMOTHY ANDREW; DIPIETRO, LAURA | Cambridge, MA | 2019 |
NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required)
NOFO Number: PA-18-573 Summary: Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of chronic pain (CP) in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of CP [25-28]. However, the most common NIBS methods, e.g., transcranial direct current stimulation, have shown limited, if any, efficacy in treating neuropathic pain. It has been postulated that limitations in conventional NIBS techniques’ focality, penetration, and targeting control limit their therapeutic efficacy . Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue . This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat CP in carpal tunnel syndrome (CTS), both as a lone treatment and in conjunction with physical therapy (PT). Investigators hypothesize ESStim can be provided synergistically with PT, as both can encourage plasticity-dependent changes which could maximally improve a CTS patient’s pain free mobility. In parallel with the CTS treatments, the team will build multivariate linear and generalized linear regression models to predict the CTS patient outcomes related to pain, physical function, and psychosocial assessments as a function of baseline disease characteristics. The computational work will be used to develop an optimized CTS ESStim dosing model. |
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1R41NS113717-01
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Pre-clinical evaluation of DT-001, a small molecule antagonist of MD2-TLR4 for utility in the treatment of pain | Cross-Cutting Research | Small Business Programs | NINDS | DOULEUR THERAPEUTICS, INC. | YAKSH, TONY L; CHAKRAVARTHY, KRISHNAN | San Diego, CA | 2019 |
NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
NOFO Number: PA-18-575 Summary: Chronic persistent post-operative pain (CPOP) is a devastating outcome from any type of surgical procedure. Its incidence is anywhere between 20-85% depending on the type of surgery, with thoracotomies showing one of the highest annual incidences of 30-60%. Given that millions of patients (approximately 23 million yearly based on incidence) are affected by CPOP, the results are increased direct medical costs, increased indirect medical costs due to decreased productivity, and associated negative effects on an individual’s physical functioning, psychological state, and quality of life. Given these extensive public health and economic consequences there is a resurgence of research in the area of preventative analgesia. The goal of this project is to evaluate a novel small molecule antagonist of MD2-TLR4, DT-001 in preclinical models of surgical pain representative of persistent post-operative pain. In collaboration with University of California, San Diego, DT-001 will be evaluated for its ability to block the development of neuropathic pain states. These studies will evaluate dose escalating efficacy of DT001 in rats in formalin and spinal nerve injury (SNI) models using both intrathecal and intravenous routes of administration. Tissues will be preserved to assess functional effects on relevant pain centers for analysis by Raft. With demonstration of efficacy, these studies will determine the optimal dose and route of administration of DT001 and guide a development path to IND and eventually clinical trials. |
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1R01DE029187-01
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LIGHT and Lymphotoxin targeting for the treatment of chronic orofacial pain conditions | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NIDCR | UNIVERSITY OF TEXAS HLTH SCIENCE CENTER | AKOPIAN, ARMEN N | San Antonio, 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: Mismanagement of orofacial chronic pain, such as temporomandibular joint and muscle disorders (TMJD) and oral cancer, substantially contributes to opioid overuse; overdose-related deaths; and cardiovascular, renal, and neurological complications at epidemic proportions. The current paradigm implies that orofacial conditions could trigger maladaptation of the immune system and plasticity supporting persistent inflammation, which influences the development and maintenance of orofacial chronic pain. LIGHT (TNFSF14) and Lymphotoxin-beta (LT?), members of the tumor necrosis factor superfamily, provide a balance between protective immunity and immunopathology during chronic inflammatory diseases. This project will test the hypothesis that targeting LIGHT and LT? signaling could prevent the development and inhibit the maintenance of chronic pain produced by TMJD and oral cancer, via peripheral mechanisms involving plasticity of immune, stromal, and tumor cells, as well as sensory neurons. The proposed research is significant as it advances our understanding of mechanisms regulating the development and maintenance of orofacial pain and offers new therapeutic targets and an immunotherapeutic approach for preventing and blocking chronic pain during TMJD and oral cancer. |
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1UG3TR003149-01
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hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception | 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 TEXAS DALLAS | BLACK, BRYAN JAMES | Dallas, TX | 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 an innovative three-dimensional (3D) model of acute and chronic nociception using human induced pluripotent stem cell (hiPSC) sensory neurons and satellite glial cell surrogates. They will develop a tissue chip for modeling acute and chronic nociception based on 3D hiPSC-based dorsal root ganglion tissue mimics and a high-content, moderate-throughput microelectrode array. Researchers will demonstrate stable spontaneous and noxious stimulus-evoked behavior in response to thermal, chemical, and electrical stimulation challenges. They aim to demonstrate sensitivity to translational control via ligand receptor interactions between neuronal and non-neuronal cell types. They also will demonstrate the quantitative efficiency and preclinical efficacy of our system by detecting known ligand-based modulators of translational control and voltage-gated ion channel antagonists in a sensitized model of chronic nociception. Researchers will leverage the high-throughput nature of our tissue chip model to screen Food and Drug Administration–approved bioactive compounds. |
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3R01NS103350-02S1
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REGULATION OF TRIGEMINAL NOCICEPTION BY TRESK CHANNELS | 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 | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: TWIK-related spinal cord K+ (TRESK) channel is abundantly expressed in all primary afferent neurons (PANs) in trigeminal ganglion (TG) and dorsal root ganglion (DRG), mediating background K+ currents and controlling the excitability of PANs. TRESK mutations cause migraine headache but not body pain in humans, suggesting that TG neurons are more vulnerable to TRESK dysfunctions. TRESK knock out (KO) mice exhibit more robust behavioral responses than wild-type controls in mouse models of trigeminal pain, especially headache. We will investigate the mechanisms through which TRESK dysfunction differentially affects TG and DRG neurons. Based on our preliminary finding that changes of endogenous TRESK activity correlate with changes of the excitability of TG neurons during estrous cycles in female mice, we will examine whether estrogen increases migraine susceptibility in women through inhibition of TRESK activity in TG neurons. We will test the hypothesis that frequent migraine attacks reduce TG TRESK currents. |
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3U19TW009872-05S1
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NOVEL THERAPEUTIC AGENTS FROM THE BACTERIAL SYMBIONTS OF BRAZILIAN INVERTEBRATES | Preclinical and Translational Research in Pain Management | FIC | HARVARD MEDICAL SCHOOL | CLARDY, JON; PUPO, MONICA T | Boston, MA | 2018 | |
NOFO Title: Limited Competition: International Cooperative Biodiversity Groups (U19)
NOFO Number: RFA-TW-13-001 Summary: An International Cooperative Biodiversity Group with an interdisciplinary leadership team of physicians, pharmacologists, evolutionary biologists, and chemists will discover and develop therapeutic agents produced by Brazilian symbiotic bacteria. The team will target three therapeutic areas: 1) infectious fungal pathogens, 2) Chagas disease and leishmaniasis, and 3) cancers of the blood. All three areas represent major threats to human health that need to be addressed with new therapeutic agents. Internationally, invasive fungal diseases kill more people than malaria or TB, while Chagas disease imposes a special burden on Brazil, killing as many Brazilians as TB. Leishmaniasis has now passed Chagas disease in the Brazilian population. Despite major improvements in cancer chemotherapy, cancer is projected to result in 8 million deaths internationally this year (13% of all deaths, WHO) and an estimated 13 million per year by 2030. |
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3U01DE025633-03S1
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INVESTIGATION AND MODULATION OF THE MU-OPIOID MECHANISM IN CHRONIC TMD (IN VIVO) | Preclinical and Translational Research in Pain Management | NIDCR | UNIVERSITY OF MICHIGAN AT ANN ARBOR | DASILVA, ALEXANDRE | ANN ARBOR, MI | 2018 | |
NOFO Title: Biology of the Temporomandibular Joint in Health and Disease (R01)
NOFO Number: PA-14-358 Summary: Initial studies using positron emission tomography (PET) with [11C] carfentanil, a selective radiotracer for ?-opioid receptor (?OR), have demonstrated that there is a decrease in thalamic µOR availability (non-displaceable binding potential BPND) in the brains of TMD patients during masseteric pain compared to healthy controls. ?-opioid neurotransmission is arguably one of the mechanisms most centrally involved in pain regulation and experience. The main goals of our study are: first, to exploit the ?-opioidergic dysfunction in vivo in TMD patients compared to healthy controls; second, to determine whether 10 daily sessions of non-invasive and precise M1 HD-tDCS have a modulatory effect on clinical and experimental pain measures in TMD patients; and third, to investigate whether repetitive active M1 HD-tDCS induces/reverts ?OR BPND changes in the thalamus and other pain-related regions and whether those changes are correlated with TMD pain measures. |
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1RF1NS113883-01
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Sympathetic-mediated sensory neuron cluster firing as a novel therapeutic 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 | JOHNS HOPKINS UNIVERSITY | DONG, XINZHONG | Baltimore, MD | 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: An important component of neuropathic pain is spontaneous or ongoing pain, such as burning pain or intermittent paroxysms of sharp and shooting pain, which may result from abnormal spontaneous activity in sensory nerves. However, due to technical limitations, spontaneous activity in sensory neurons in vivo has not been well studied. Using in vivo imaging in genetically-modified mice, preliminary findings identified spontaneously-firing clusters of neurons formed within the dorsal root ganglia (DRG) after traumatic nerve injury that exhibits increased spontaneous pain behaviors. Furthermore, preliminary evidence has been collected that cluster firing may be related to abnormal sympathetic sprouting in the sensory ganglia. This project will test the hypothesis that cluster firing is triggered by abnormal sympathetic inputs to sensory neurons, and that it underpins spontaneous paroxysmal pain in neuropathic pain models. Findings from this project will identify potential novel therapeutic targets for the treatment of neuropathic pain. |
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1UG3TR003090-01
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Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets, and an Empirical Strategy for Personalized Pain Management | 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 PITTSBURGH AT PITTSBURGH | GOLD, MICHAEL S (contact); LIN, HANG | Pittsburgh, PA | 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: The research team developed an in vitro multi-component joint on a chip (microJoint), in which engineered osteochondral complexes, synovium, and adipose tissues were integrated. This study will introduce sensory innervation into the microJoint and a neuron-containing microfluidic ally will be developed to innervate the microJoint. The osteoarthritis (OA) model will be created in the Neu-microJoint system. The research team will assess activation and/or sensitization of nociceptive afferents with electrophysiology, as well as neurite outgrowth. They will mechanically insult the Neu-microJoint and assess the emergence of “pain” in response to prolonged mechanical stress. Researchers will assess the impact of drugs used clinically for management of OA on OA models and will then use “omic” approaches to identify new biomarkers and therapeutic targets. Researchers will assess the impact of opioids—which they hypothesize will increase the rate of joint degeneration and potentiate the release of pain-producing mediators—on neural activity in the presence and absence of joint injury, as well as the integrity of all joint elements. |