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 # Sort ascending | Project Title | Research Focus Area | Research Program | Administering IC | Institution(s) | Investigator(s) | Location(s) | Year Awarded |
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3R44DA044053-03S1 | DEVELOPMENT AND EVALUATION OF VIDEO-BASED DIRECTLY OBSERVED THERAPY FOR OFFICE-BASED TREATMENT OF OPIOID USE DISORDERS WITH BUPRENORPHINE | Cross-Cutting Research | Small Business Programs | NIDA | emocha Mobile Health, Inc. | Seiguer, Sebastian | Owings Mills, MD | 2019 |
NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-16-302 Summary: Since 2002, persons with opioid use disorders who desire medication-assisted treatment can be treated with buprenorphine, which has been shown to be efficacious. Buprenorphine treatment can occur in any medical office-based setting, is prescribed by any physician who seeks to become waivered, and is taken by patients at home unsupervised. However, without visual confirmation of medication ingestion, providers remain unsure if patients divert part or all of their buprenorphine medication. This project will develop the technical and logistical workflow needed to implement a video-based application, miDOT, for office-based buprenorphine monitoring during the initial months of care, which will allow health care providers to monitor whether patients ingest the drug and adhere to treatment. The project will configure a video-based DOT platform, evaluate its effectiveness in securing medication ingestion and care retention for illicit opiate users, and solidify routes of sustainable commercial viability with commercial partners. |
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3R44DA044053-02S1 | DEVELOPMENT AND EVALUATION OF VIDEO-BASED DIRECTLY OBSERVED THERAPY FOR OFFICE-BASED TREATMENT OF OPIOID USE DISORDERS WITH BUPRENORPHINE | Cross-Cutting Research | Small Business Programs | NIDA | emocha Mobile Health, Inc. | Seiguer, Sebastian | Owings Mills, MD | 2019 |
NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-16-302 Summary: Since 2002, persons with opioid use disorders who desire medication-assisted treatment can be treated with buprenorphine, which has been shown to be efficacious. Buprenorphine treatment can occur in any medical office-based setting, is prescribed by any physician who seeks to become waivered, and is taken by patients at home unsupervised. However, without visual confirmation of medication ingestion, providers remain unsure if patients divert part or all of their buprenorphine medication. This project will develop the technical and logistical workflow needed to implement a video-based application, miDOT, for office-based buprenorphine monitoring during the initial months of care, which will allow health care providers to monitor whether patients ingest the drug and adhere to treatment. The project will configure a video-based DOT platform, evaluate its effectiveness in securing medication ingestion and care retention for illicit opiate users, and solidify routes of sustainable commercial viability with commercial partners. |
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3R42TR001270-03S1 | PERIPHERAL NERVE-ON-A-CHIP FOR PREDICTIVE PRECLINICAL PHARMACEUTICAL TESTING | Cross-Cutting Research | Small Business Programs | NCATS | AXOSIM, INC. | CURLEY, JABE L; MOORE, MICHAEL J | NEW ORLEANS, LA | 2018 |
NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42])
NOFO Number: PA-16-303 Summary: The ability to de-risk lead compounds during pre-clinical development with advanced “organoid-on-a-chip” technologies shows promise. Development of microphysiological models of the peripheral nervous system is lagging. The technology described herein allows for 3D growth of high-density axonal fiber tracts, resembling peripheral nerve anatomy. The use of structural and functional analyses should mean drug-induced neural toxicity will manifest in these measurements in ways that mimic clinical neuropathology. The goals of this proposal are to establish our human model using relevant physiological measurements in tissues fabricated from human iPS cells and to validate the model system with a library of compounds, comparing against conventional cell culture models. Validating the peripheral nerve model system with drugs known to induce toxicity via a range of mechanisms will demonstrate the ability of the system to predict various classifications of neuropathy, yielding a high-content assay far more informative than traditional in vitro systems. |
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3R42HD088325-02A1S1 | Mobile Augmented Screening Tool to Increase Adolescent HIV Testing and Linkage to Care | Cross-Cutting Research | Small Business Programs | NIDA | DIGITAL HEALTH EMPOWERMENT, INC. | ARONSON, IAN DAVID | BROOKLYN, NY | 2019 |
NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-16-302 Summary: Adolescents face increased HIV risk, infrequent testing, inconsistent linkage to care, and a lack of prevention-related knowledge. We propose to complete and evaluate the Mobile Augmented Screening (MAS) tool to privately and discretely offer routine HIV testing and counseling, including prevention education, to high-need, diverse adolescent and young adult populations at a low cost. The MAS will consist of a tablet-based intervention including a brief video designed to increase adolescent HIV testing, automated text messages to facilitate linkage to care for those who test positive, and text-based education for those who test negative or decline testing. Phase I was conducted with young emergency department (ED) patients. Preliminary evaluations indicate the video led to significant knowledge increases and encouraged testing. In phase II, we seek to complete intervention development and evaluate through a randomized controlled trial with ED patients, with qualitative interviews for a subset of young patients and ED staff. |
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3R37DA047926-02S1 | Social networks of young American Indian adolescents and their parents:Characteristics, connections, and response to intervention | New Strategies to Prevent and Treat Opioid Addiction | Preventing Opioid Use Disorder | NIDA | UNIVERSITY OF COLORADO DENVER | WHITESELL, NANCY RUMBAUGH | Aurora, CO | 2020 |
NOFO Title: Notice of Special Interest(NOSI): HEAL Initiative: Social Network Analyses to Reduce American Indian and Alaska Native Opioid Use Disorder and Related Risks for Suicide and Mental Health Disorders
NOFO Number: NOT-DA-20-033 |
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3R37DA020686-13S1 | 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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3R35NS105092-03S1 | The biophysics of skin-neuron sensory tactile organs and their sensitivity to mechanical and chemical stress | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | STANFORD UNIVERSITY | GOODMAN, MIRIAM B | Palo Alto, CA | 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: This project will establish a rapid research pipeline for linking plant-derived compounds to nociception (pain) and to G Protein-Coupled Receptors (GPCRs) and ion channels in the druggable human genome. As more than 80% of these membrane proteins are conserved in the C. elegans nematodes, the study will screen for compounds and genes affecting nociception as well as to identify novel ligand-receptor pairs using this model organism. The study will test which understudied GPCRs and ion channels are involved in nociception as well as attraction or repulsion behaviors. This research has the potential to reveal novel ligand-receptor pairs that could serve as new entry points for improved or alternative pain treatments. |
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3R34AA025480-02S1 | IMPLEMENTING MEDICATION-ASSISTED THERAPY FOR SUBSTANCE USE DISORDERS IN MENTAL HEALTH | New Strategies to Prevent and Treat Opioid Addiction | Optimizing Care for People with Opioid Use Disorder and Mental Health Conditions | NIAAA | Rand Corporation | WATKINS, KATHERINE E | SANTA MONICA, CA | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Substance use disorders (SUDs) can have devastating consequences for people with serious mental illness (SMI). SUDs can increase morbidity and mortality and are associated with higher healthcare and social costs, homelessness, and incarceration. Unfortunately, despite the availability of effective treatments, most individuals with co-occurring SMI and SUD (COD) never receive SUD treatment. We propose to evaluate system, provider, and patient-level facilitators and barriers and develop an implementation strategy and toolkit to promote the use of medication-assisted treatment (MAT) for people with COD. Aims 1–3 seek to assess organizational capacity (at the system and provider level); organizational readiness (at the provider level); and perceived needs, attitudes, and preferences (at the patient level) to identify barriers and facilitators. In Aim 4, we will use findings from Aims 1–3 to guide development of the implementation strategy and toolkit, using stakeholder input and a systematic process for strategy development. |
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3R33AT010606-03S1 | Adapting the HOPE Online Support Intervention to Increase MAT Uptake Among OUD Patients | Translation of Research to Practice for the Treatment of Opioid Addiction | Behavioral Research to Improve Medication-Based Treatment | NCCIH | UNIVERSITY OF CALIFORNIA-IRVINE | YOUNG, SEAN | Irvine, CA | 2021 |
NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025 Summary: Effective medications for opioid use disorder (MOUD) are approved by the Food and Drug Administration for the treatment of people with opioid use disorder; however, only a small fraction of patients who would benefit from these medications actually use them. Several reasons contribute to low MOUD use, including lack of insurance; lack of knowledge about the medications, both among patients and providers; stigma associated with MOUD; and social norms. Innovative methods are needed to help increase MOUD use. One such option is peer-led interventions that might increase patients’ interest in MOUD. One existing peer-led intervention is the Harnessing Online Peer Education (HOPE) online community intervention that has been designed to reduce stigma and increase health behavior change among stigmatized populations, such as people living with HIV. This project will investigate whether and how HOPE can be adapted for people with opioid use disorder. It will assess whether HOPE can effectively increase MOUD requests, MOUD uptake, and sustained adherence to MOUD as well as reduce overdose rates. |
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3R24DA055306-01S1 | Wake Forest IMPOWR Dissemination Education and Coordination Center (IDEA-CC) | Cross-Cutting Research | Leveraging Existing and Real-Time Opioid and Pain Management Data | NIDA | WAKE FOREST UNIVERSITY HEALTH SCIENCES | ADAMS, MEREDITH C B | Winston-Salem, NC | 2022 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-20-272 Summary: This research provides support to strengthen data management, data sharing, and data readiness efforts within the HEAL Initiative. This support further fosters collaboration among HEAL awardees and enables maximal data discoverability, interoperability, and reuse by aligning with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. It also provides an opportunity for existing HEAL Initiative award recipients to increase data “FAIR”-ness, participate in coordinated HEAL Initiative activities to build community around data sharing, and foster sustainability of HEAL Initiative digital assets. |
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3R24DA051946-01S1 | CoARS Administrative Supplement | Translation of Research to Practice for the Treatment of Opioid Addiction | Recovery Research Networks | NIDA | PARTNERSHIP TO END ADDICTION | HOGUE, AARON | New York, NY | 2022 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent admin Supp Clinical Trial Optional)
NOFO Number: PA-20-272 Summary: The science of recovery support services for individuals choosing to take medications for opioid use disorder as part of their recovery pathway is gaining momentum and will benefit from a dedicated, sustainable cross-project research infrastructure. This project enhances research in the existing Consortium on Addiction Recovery Research Science. This effort coordinates varied research and training efforts across recovery support research projects, amplifies communication and dissemination channels for their activities, and is organizing the first national meetings on addiction recovery support services science. |
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3R21MD011767-02S1 | SUPPLEMENT TO OPIOID PRESCRIBING DISPARITIES IN A PUBLIC HEALTH CRISIS | Clinical Research in Pain Management | NIMHD | Research at Nationwide Children's - Nationwide Children's Hospital | CHISOLM, DEENA; DEANS, KATHERINE J | Columbus, OH | 2018 | |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: African American adults are less likely to receive analgesics, particularly opioids. Research in the pediatric surgical population is limited, but the pattern of disparate use of opioids appears consistent with adults. Furthermore, adolescent access to prescribed opioids has increased, both through physician prescribing and misuse of medications prescribed to family members or friends. This study will explore the interrelated impacts of policy, clinical need, and sociodemographic factors by combining Medicaid claims and electronic health record data with findings from a statewide opioid policy inventory. We will focus on discharge prescribing of opioids in three high-volume pediatric surgical procedures: tonsillectomy/adenoidectomy, supracondylar fracture, and appendectomy. We aim to 1) determine the extent of racial disparities in postoperative discharge opioid prescribing since the 2011 onset of enhanced opioid prescription reduction activities and 2) develop an expanded model to assess the linkage between differential opioid use for pediatric postoperative pain and opioid use-related outcomes. |
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3R21DA045092-01A1S1 | EVALUATING COGNITIVE AND DEVELOPMENTAL RISK FACTORS FOR OPIOID MISUSE AMONG ADOLESCENT CANNABIS USERS | New Strategies to Prevent and Treat Opioid Addiction | Preventing Opioid Use Disorder | NIDA | University of Washington | RAMIREZ, JASON | Seattle, WA | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: The opioid epidemic continues unabated in the United States, and despite the rapid expansion of this crisis, the nature of the risk factors that contribute to opioid misuse remain poorly understood compared with other substances of abuse. The goal of this project is to examine cannabis use and cannabis identification measures as risk factors for opioid misuse while also developing and evaluating novel implicit measures of opioid associations as risk factors for opioid misuse among an at-risk sample of adolescents. Findings from the proposed research are intended to improve the prediction of opioid misuse among adolescents and to potentially identify novel targets for prevention and intervention strategies that aim to combat the opioid epidemic. |
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3R21DA044443-02S1 | DAT-OPTIMIZING THE IMPACT OF MEDICATION ASSISTED TREATMENT INTERVENTIONS IN PRISON AND JAIL SETTINGS | Translation of Research to Practice for the Treatment of Opioid Addiction | NIDA | MIRIAM HOSPITAL | RICH, JOSIAH D | Providence, RI | 2018 | |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: We propose to estimate the impact of expanded access to medication-assisted treatment (MAT) in prisons and jails on post-release rates of overdose. Our approach will use agent-based modeling, data collected through the parent study, existing surveillance data, and recently published data from similar settings to understand how different MAT interventions in the prison and jail setting impact overdose death post-release. We will examine the impact of standard of care/no intervention, providing access to depot-naltrexone alone, providing access to all three MATs to only those who were prescribed it prior to incarceration, and comprehensive provision of all three MATs on post-release rates of overdose. These models will incorporate advanced methodological techniques that will allow for the investigation of engaged treatment, program attrition, and other complex events on a population level. This study’s findings may be used by health agencies, policymakers, and correctional systems to inform their efforts to expand MAT access. |
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3R21DA041489-02S1 | IMPROVING ACCESS TO PHARMACOTHERAPY FOR OPIOID USE DISORDER AMONG JUSTICE INVOLVED VETERANS | Translation of Research to Practice for the Treatment of Opioid Addiction | NIDA | PALO ALTO VETERANS INSTIT FOR RESEARCH | FINLAY, ANDREA K | Palo Alto, CA | 2018 | |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Justice-involved veterans have lower access to opioid use disorder (OUD) pharmacotherapy and need an effective transition from the justice system to the Department of Veterans Affairs (VA) and community health care systems to improve drug addiction treatment and outcomes. We will quantitatively evaluate patient and facility characteristics associated with differences in receipt of OUD pharmacotherapy among justice-involved veterans compared with non-justice-involved veterans and within-facility changes over time; qualitatively identify drivers of higher or lower access to OUD pharmacotherapy among justice-involved veterans compared with other veterans with OUD at the same facility; evaluate stakeholders’ perceptions of factors that explain within-facility changes in access to OUD pharmacotherapy over time; and develop and conduct a formative evaluation of implementation strategies to improve access to OUD pharmacotherapy. Results will be used to design and select implementation strategies that address identified barriers to improve access to OUD pharmacotherapy for justice-involved veterans. |
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3R01NS118563-01A1S1 | Diversity Supplement to FKBP51 Antagonism to Prevent Chronic Pain: Optimizing Efficacy & Evaluating Safety and Mechanisms | Cross-Cutting Research | Training the Next Generation of Researchers in HEAL | NINDS | UNIV OF NORTH CAROLINA CHAPEL HILL | LINNSTAEDT, SARAH; MCLEAN, SAMUEL A | Chapel Hill, NC | 2022 |
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107; PA-21-071 Summary: Current evidence indicates that chronic pain after a traumatic injury is influenced by the body’s response to stress. This project will conduct a comprehensive analysis of gene expression after traumatic stress exposure in a range of animal models in various body regions including the brain (amygdala, hippocampus, hypothalamus) and spinal cord, as well as nerves and immune cells throughout the body. These studies will be conducted in animals with no stress exposure as well as in animals treated with a molecule (FKBP51) known to block the stress response. This research will enhance understanding of how FKBP51 and post-injury stress affect pain processes. |
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3R01NS113257-01S1 | Isolation of GPR160 for biochemical analysis of the activation mechanism and development of a high throughput screening assay to identify small molecule inhibitors | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | SAINT LOUIS UNIVERSITY | SALVEMINI, DANIELA | Saint Louis, MO | 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: Neuropathic pain conditions are difficult to treat, and novel non-narcotic analgesics are desperately needed. The G protein-coupled receptor 160 (GPR160) has emerged as a novel target for analgesic development, as GPR160 in the spinal cord may play a role in the transition from acute to chronic pain. Cocaine- and Amphetamine-Regulated transcript peptide (CARTp) was identified as a ligand for GPR160. Blocking endogenous CARTp signaling in the spinal cord attenuates neuropathic pain, whereas intrathecal injection of CARTp evokes painful hypersensitivity in rodents through GPR160-dependent extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding pathways (CREB). This project will isolate and biochemically characterize GPR160 and establish methods for biochemical characterization of GPR160 interaction with CARTp activator. Researchers will miniaturize and optimize biochemical assay and scale up protein production for future high throughput biochemical screening to identify potent inhibitors of GPR160 activation. These studies are critical for defining the molecular mechanism of CARTp/GPR160 interactions and initiating large-scale screens for new inhibitors to develop novel therapeutics. |
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3R01NS111929-01A1S1 | Anatomic, Physiologic and Transcriptomic Mechanisms of Neuropathic Pain in Human DRG | 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 | DOUGHERTY, PATRICK M | Houston, TX | 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: Using neural tissues from pain patients, this project will investigate mechanisms of neuronal and/or immune dysfunction driving chronic pain. The researchers will use spatial transcriptomics on human dorsal root ganglion (DRG) and spinal cord tissues to examine the cellular expression profile for these targets using the 10X Genomics Visium technology. The use of tissues from control surgical patients and organ donors as well as surgical patients with neuropathic pain will enable validation of expression of these targets in human tissue as well as indication of their potential involvement in neuropathic pain. This collaborative effort will use DRGs removed from pain-phenotyped patients during neurological surgery, as well as lumbar DRGs and spinal cord from organ donors. This study will map the spatial transcriptomes at approximately single cell resolution in the human DRG and spinal cord. |
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3R01NS103350-02S1 | 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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3R01NS102432-02S1 | 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 | UNIVERSITY OF CALIFORNIA, SAN DIEGO | MILLER, YURY; YAKSH, TONY L. | LA JOLLA, CA | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 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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3R01NS098826-02S1 | PROTEASE ACTIVATED RECEPTOR TYPE 2 TARGETING FOR MIGRAINE PAIN | Preclinical and Translational Research in Pain Management | NINDS | UNIVERSITY OF TEXAS DALLAS | PRICE, THEODORE J; BOITANO, SCOTT; DUSSOR, GREGORY O; VAGNER, JOSEF | RICHARDSON, TX | 2018 | |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Migraine is the most common neurological disorder. Currently available treatments fail to effectively manage migraine in most patients. Development of new therapeutics has been slow due in large part to a poor understanding of the underlying pathology of migraine. Endogenous proteases, released in the meninges by resident mast cells, have been proposed as a potential driver of migraine pain via an action on protease activated receptor type 2 (PAR2). The central hypothesis is that PAR2 expression in nociceptors that project to the meninges plays a key role in the pathogenesis of migraine pain. The aims are to: 1) use the established PAR2 development pipeline to design new PAR2 antagonists with improved drug-like properties; 2) use pharmacological tools in a novel mouse migraine model to further understand the potential role of PAR2 in migraine; and 3) use mouse genetics to study the cell type–specific role of PAR2 in migraine pain. |
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3R01NS097880-02S1 | VALIDATION OF TARGETING MACROPHAGE-MEDIATED EVENTS IN THE DRG TO ALLEVIATE CHRONIC SPINAL CORD INJURY PAIN | 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 | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Spinal cord injury (SCI) impairs sensory transmission and leads to chronic, debilitating neuropathic pain. While our understanding of the development of chronic pain has improved, the available therapeutics provide limited relief. We will examine the peripheral immune and inflammatory response. Secondary inflammation in response to SCI is a series of temporally ordered events: an acute, transient upregulation of chemokines, followed by the recruitment of monocytes/macrophages and generation of an inflammatory environment at the lesion site in the spinal cord, but also surrounding primary nociceptors in the dorsal root ganglia (DRG). These events precede neuropathic pain development. Previous work indicates that after SCI, macrophage presence in the DRG correlates with neuropathic pain. We propose to study: 1) whether the phenotype of macrophages that infiltrate the DRG is different than those that persist chronically after SCI and 2) how manipulation of macrophage phenotype affects nociceptor activity and pain development. |
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3R01NS094461-04S2 | TARGETING SPECIFIC INTERACTIONS BETWEEN A-KINASE ANCHORING PROTEINS (AKAPS) AND ION CHANNELS WITH CELL-PERMEANT PEPTIDES AS A NOVEL MODE OF THERAPEUTIC INTERVENTION AGAINST PAIN DISORDERS | Preclinical and Translational Research in Pain Management | Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain | NINDS | UNIVERSITY OF TEXAS HLTH SCIENCE CENTER | SHAPIRO, MARK S | SAN ANTONIO, TX | 2019 |
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591 Summary: Multi-protein complexes have emerged as a mechanism for spatiotemporal specificity and efficiency in the function and regulation of myriad cellular signals. In particular, many ion channels are clustered either with the receptors that modulate them, or with other ion channels whose activities are linked. Often the clustering is mediated by scaffolding proteins, such as the AKAP79/150 protein that is a focus of this research. This research will focus on three different channels critical to nervous function. One is the"M-type" (KCNQ, Kv7) K+ channel that plays fundamental roles in the regulation of excitability in nerve and muscle. It is thought to associate with Gq/11- coupled receptors, protein kinases, calcineurin (CaN), calmodulin (CaM) and phosphoinositides via AKAP79/150. Another channel of focus is TRPV1, a nociceptive channel in sensory neurons that is also thought to be regulated by signaling proteins recruited by AKAP79/150. The third are L-type Ca2+ (CaV1.2) channels that are critical to synaptic plasticity, gene regulation and neuronal firing. This research will probe complexes containing AKAP79/150 and these three channels using"super-resolution" STORM imaging of primary sensory neurons and heterologously-expressed tissue-culture cells, in which individual complexes can be visualized at 10-20 nm resolution with visible light, breaking the diffraction barrier of physics. The researchers hypothesize that AKAP79/150 brings several of these channels together to enable functional coupling, which the researchers will examine by patch-clamp electrophysiology of the neurons. Förster resonance energy transfer (FRET) will also be performed under total internal reflection fluorescence (TIRF) or confocal microscopy, further testing for complexes containing KCNQ, TRPV1 and CaV1.2 channels. Since all three of these channels bind to AKAP79/150, the researchers hypothesize that they co-assemble into complexes in neurons, together with certain G protein-coupled receptors. Furthermore, the researchers hypothesize these complexes to not be static, but rather to be dynamically regulated by other cellular signals, which the researchers will examine using rapid activation of kinases or phosphatases. Several types of mouse colonies of genetically altered AKAP150 knock-out or knock-in mice will be utilized. |
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3R01NS093990-04S1 | S1P RECEPTOR MECHANISMS IN NEUROPATHIC PAIN | Preclinical and Translational Research in Pain Management | NINDS | VIRGINIA COMMONWEALTH UNIVERSITY | SIM-SELLEY, LAURA J; HAUSER, KURT F; LICHTMAN, ARON H; SELLEY, DANA E | RICHMOND, VA | 2018 | |
NOFO Title: Mechanisms, Models, Measurement, & Management in Pain Research (R01)
NOFO Number: PA-13-118 Summary: Chronic pain diminishes the quality of life for millions of patients, and new drugs that have better efficacy and/or fewer side effects are needed. A promising target is the sphingosine-1-phosphate (S1P) receptor system, which mediates central nervous system (CNS) neuromodulatory functions. FTY720-phosphate, the active metabolite of FTY720 (FTY), acts as an agonist at four of the five S1P receptors (S1P1, 3, 4, 5). We propose that the S1P1 receptor is a target for treatment of neuropathic pain. We will test whether S1P1 receptors mediate anti-hyperalgesic effects in a mouse neuropathic pain model. The specific aims are to: 1) determine the role of S1P1Rs in alleviation of neuropathic pain by S1PR ligands; 2) determine the role of FTY-induced S1PR adaptation in FTY-mediated reversal of neuropathic pain; and 3) determine the role of S1P and S1P1 receptors in spinal glia in CCI-induced neuropathic pain and its reversal by FTY. |
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3R01NS045594-14S1 | 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. |