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.

Reset
Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
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.
1U19NS130608-01
Human Nociceptor and Spinal Cord Molecular Signature Center Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TEXAS DALLAS PRICE, THEODORE J (contact); CURATOLO, MICHELE; DOUGHERTY, PATRICK M Richardson, TX 2023
NOFO Title: Notice of Special Interest (NOSI): Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Support Career Enhancement Related to Clinical Research on Pain
NOFO Number: NOT-NS-22-087
Summary:

This project supports a post-baccalaureate trainee develop skills needed to pursue a career in clinical pain research. The research will use molecular tools to study nerve, joint, muscle, and fascia tissues from individuals with chronic low back pain who had spine surgery. The research will include working with patients, designing clinical studies, and sharing results. 
3UG3TR003149-02S1
Supplement to 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 Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCATS UNIVERSITY OF TEXAS DALLAS BLACK, BRYAN JAMES Dallas, 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:

This study aims to determine whether a subset of understudied genes that are expressed in human and mouse dorsal root ganglia (DRG) tissues (critical for relaying the sensation of pain from the body to the central nervous system), are also expressed in human induced pluripotent stem cell DRG mimetics. The study will also determine if these genes are involved in neuronal excitability changes under inflammatory conditions and compare these responses to those of primary DRG neurons. Third and finally, the study will optimize genetic depletion of target genes enabling future fundamental and preclinical research studies.
1UG3TR003149-01
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.
1R61NS113329-01
Discovery of Biomarker Signatures Prognostic for Neuropathic Pain after Acute Spinal Cord Injury Preclinical and Translational Research in Pain Management Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions NINDS UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON HERGENROEDER, GEORGENE W Houston, TX 2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Debilitating neuropathic pain occurs in 40 percent to 70 percent of people who suffer from spinal cord injury (SCI). There are no distinguishing characteristics to identify who will develop neuropathic pain. The objective of this research is to develop a biomarker signature prognostic of SCI-induced neuropathic pain (NP). The aims of the project are to (1) identify autoantibodies in plasma samples from acute SCI patients to CNS autoantigens and determine the relationship between autoantibodies levels to the development of NP, (2) identify the autoantibody combination with maximal prognostic accuracy for the development of NP at six months after SCI, and (3) develop and optimize an assay to simultaneously measure several autoantibodies and independently validate the prognostic efficacy for NP using plasma samples collected prospectively. Establishing a panel will refine the prognostic value of these autoantibodies as biomarkers to detect who are vulnerable to NP and may be used to for development of nonaddictive pain therapeutics.
5R01NS094461-04
Clustering of individual and diverse ion channels together into complexes, and their functional coupling, mediated by A-kinase anchoring protein 79/150 in neurons 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 SCI CTR SAN ANTONIO SHAPIRO, MARK S San Antonio, TX 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Multi-protein complexes have emerged as a mechanism for spatiotemporal specificity and efficiency in the function and regulation of cellular signals. 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 AKAP79/150. We will probe complexes containing AKAP79/150 and three different channels critical to nervous function: KCNQ/Kv7, TRPV1, and CaV1.2. We will use"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. We hypothesize that AKAP79/150 brings several of these channels together to enable functional coupling, which we will examine by patch-clamp electrophysiology of the neurons. Since all three of these channels bind to AKAP79/150, we hypothesize that they co-assemble into complexes in neurons and that they are dynamically regulated by other cellular signals.
3R01DE029187-01S2
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 NINDS UNIVERSITY OF TEXAS HLTH SCIENCE CENTER AKOPIAN, ARMEN N; RUPAREL, SHIVANI B; TUMANOV, ALEXEI V San Antonio, TX 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:

Chronic orofacial pain during Temporomandibular Disorders (TMD) and oral cancer is a significant health problem with scarce non-opioid treatment options. This study aims to validate critical regulators of the balance between protective immunity and immunopathology during chronic inflammatory diseases?tumor necrosis factor alpha superfamily members, LIGHT (TNFSF14) and lymphotoxin-beta (LT?) and their receptors, LT?R and Herpes Virus Entry Mediator (HVEM)?as novel therapeutic targets. The study also seeks to determine whether inhibition of LIGHT and LT? signaling prevents the development and inhibits maintenance of chronic TMD and oral cancer pain via peripheral mechanisms involving plasticity of immune, muscle and tumor cells as well as sensory neurons. The study will define the contribution of LIGHT and LT? signaling to TMD-induced excitability of trigeminal sensory neurons innervating the masseter muscle and joint. New validated therapeutic targets for prevention and treatment of orofacial pain that can be peripherally targeted would reduce side effects of current pain medicates related to drug dependence or tolerance.
5R01DA038645-05
KOR AGONIST FUNCTIONAL SELECTIVITY IN PERIPHERAL SENSORY NEURONS Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDA UNIVERSITY OF TEXAS HLTH SCIENCE CENTER CLARKE, WILLIAM P; BERG, KELLY ANN 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:

Functional selectivity is a term used to describe the ability of drugs to differentially regulate the activity of multiple signaling cascades coupled to the receptor. The underlying mechanism for functional selectivity is based upon the formation of ligand-specific receptor conformations that are dependent upon ligand structure. Functional selectivity has the potential to revitalize the drug discovery/development process. Ligands with high efficacy for specific signaling pathways (or specific patterns of signaling) that mediate beneficial effects, and with minimal activity at pathways that lead to adverse effects, are expected to have improved therapeutic efficacy. We propose to demonstrate that ligand efficacy for specific signaling pathways associated with antinociception can be finely tuned by structural modifications to a ligand. We propose to use U50,488 and Salvinorin-A (Sal-A) as scaffolds to develop functionally selective analogs that maintain high efficacy for signaling pathways that lead to antinociception and minimize activity toward anti-antinociceptive signaling pathways.
1R01DE029187-01
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.
1UC2AR082195-01
Comprehensive Functional Phenotyping of Trigeminal Neurons Innervating Temporomandibular Joint (TMJ) Tissues in Male, Female and Aged Mice, Primates, and Humans With and Without TMJ Disorders (TMJD) Preclinical and Translational Research in Pain Management Restoring Joint Health and Function to Reduce Pain (RE-JOIN) NIAMS UNIVERSITY OF TEXAS HLTH SCIENCE CENTER AKOPIAN, ARMEN N; BOADA, MARIO DANILO; ERNBERG, MALIN; MACPHERSON, LINDSEY J San Antonio, TX 2022
NOFO Title: HEAL Initiative: Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN) (UC2 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-22-009
Summary:

Scientists do not know the details of how the nervous system interacts with the temporomandibular joint (TMJ) that connects the lower jaw with the skull. This project aims to comprehensively explain the functions, types, neuroanatomical distributions, and adaptability (plasticity) of specific nerve cells in the brain (trigeminal neurons) that connect with the TMJ. The research will analyze nerve-TMJ connections associated with chewing muscles and other structures that form the TMJ such as cartilage and ligaments. The project will analyze samples from both sexes of aged mice, primates, and humans with and without painful TMJ disorders. This research aims to uncover potential treatment and prevention targets for managing TMJ pain.
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.
1RM1NS128787-01
Understanding the Mechanistic, Neurophysiological, and Antinociceptive Effects of Transcutaneous Auricular Neurostimulation for Treatment of Chronic Pain Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NINDS University of Texas Med BR WILKES, DENISE (contact); BADRAN, BASHAR W; HOUGHTON, DAVID C; KHODAPARAST, NAVID Galveston, TX 2022
NOFO Title: HEAL Initiative: Interdisciplinary Teams to Elucidate the Mechanisms of Device-Based Pain Relief (RM1 Clinical Trial Optional)
NOFO Number: NS22-016
Summary:

Despite the need for non-opioid treatments for chronic pain, few alternative treatment approaches exist. Transcutaneous auricular neurostimulation (tAN) is a safe and effective treatment for pain during opioid withdrawal; however, researchers do not understand how tAN reduces pain, which limits its clinical use. A better understanding of how tAN affects neurophysiological processes to provide pain relief would likely expand tAN development and use. This interdisciplinary project will conduct research in both healthy adults and those with chronic pain to explain the neurochemical and neurophysiological mechanisms for tAN-based pain relief, and also help optimize treatments and their use.
1R61NS127286-01
Developing GPR37 Activators as Non-Opioid Pain Therapeutics Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS University of Texas Med BR LA, JUN-HO (contact); ALLEN, JOHN A; ZHOU, JIA Galveston, TX 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Chronic pain from tissue injury often stems from long-term changes in spinal cord circuits that change nerve sensation. Reversing these changes may provide better pain therapeutics. Previous work in animal models showed that activating G protein-coupled receptor 37 (GPR37) dampens nerve signal intensity after long-term stimulation and alleviates pain behavioral responses. This project aims to validate GPR37 in the spinal cord as a useful target for new treatments for neuropathic pain. The work will facilitate screening and identification of new molecules that activate GPR37, which can then be tested for efficacy and safety in further research in animal models of pain.
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.
1RF1NS113256-01
Dnmt3a as an epigenetic target for chronic pain treatment Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TX MD ANDERSON CAN CTR PAN, ZHIZHONG Z Houston, TX 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

It is unclear what changes in the brain mediate the development of chronic pain from acute pain and how chronic pain may change responses to opioid reward for the altered liability of opioid abuse under chronic pain. Preliminary studies have found that Dnmt3a, a DNA methyltransferase that catalyzes DNA methylation for gene repression, is significantly downregulated in the brain in a time-dependent manner during the development of chronic pain and after repeated opioid treatment. This project will investigate whether Dnmt3a acts as a key protein in the brain for the development of chronic pain, and whether Dnmt3a could be a novel epigenetic target for the development of new drugs and therapeutic options for the treatment of chronic pain while decreasing abuse liability of opioids.
1UG3NS127251-01A1
Development of Pathology-Activated Drugs for Treatment of Neuropathic Pain Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF TX MD ANDERSON CAN CTR GRACE, PETER M (contact); ABELL, ANDREW Houston, TX 2022
NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010
Summary:

The medication monomethyl fumarate, approved for treating multiple sclerosis, has pain-relieving properties, but it also has side effects that affect the digestive tract and decrease levels of white blood cells, a problem known as leukopenia. This project will limit the availability of monomethyl fumarate to areas in the central nervous system associated with pain. Targeting the delivery of this drug to pain-related regions may improve its safety profile for treating neuropathic pain.
1R01NS116704-01
Validation of Fibroblast-Derived PI16 as a Novel Target for pain Treatment Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF TX MD ANDERSON CAN CTR KAVELAARS, ANNEMIEKE; HEIJNEN, COBI J Houston, TX 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:

This project aims to validate Peptidase Inhibitor 16 (PI16) as a novel target for the treatment of chronic pain using mouse models and tissues of human patients with neuropathy. PI16 was identified as a novel regulator of chronic pain in preclinical bench studies. PI16 is a small molecule that has not been studied in the context of pain. Mice that are deficient for PI16 function are protected against mechanical allodynia (tactile pain from light touch) in spared nerve injury (SNI) and paclitaxel models of neuropathic pain. PI16 is only detectable in fibroblasts around peripheral nerves (perineurium), and in the meninges of dorsal root ganglia (DRG), spinal cord, and brain, but not in neurons, glia or leukocytes. PI16 levels in perineurial and DRG meningeal fibroblasts increase during neuropathic pain. Increased PI16 secretion by DRG meningeal and perineurial fibroblasts may promote chronic pain by increasing blood nerve barrier (BNB) permeability and leukocyte trafficking into nerve and DRG.
1RF1NS113840-01
Nrf2 Activation for Addiction-Free Treatment 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 TX MD ANDERSON CAN CTR GRACE, PETER MICHAEL Houston, TX 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Effective treatments are elusive for the majority of patients with neuropathic pain. Reactive oxygen and nitrogen species (ROS/RNS) are involved in neuropathic pain, because they drive mitochondrial dysfunction, cytokine production, and neuronal hyperexcitability; therefore, stimulation of endogenous antioxidants is predicted to simultaneously resolve multiple neuropathic pain mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that is a potential therapeutic target because it regulates the expression of a large number of endogenous antioxidant-related genes and can be activated with a single drug. This project will test the hypothesis that Nrf2 activation increases multiple endogenous antioxidants, therefore reversing neuropathic pain behaviors and counteracting neuropathic pain mechanisms that are driven by ROS/RNS and could provide an effective pain therapy, with minimal abuse/addictive potential.
1U18EB030607-01
Non-invasive Nonpharmaceutical Treatment for Neck Pain: Development of Cervical Spine-specific MR-guided Focused Ultrasound System Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NINDS UNIVERSITY OF UTAH RIEKE, VIOLA Salt Lake City, UT 2020
NOFO Title: HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-18-003
Summary:

Neck pain is the fourth leading cause of disability and also a significant cause of cervicogenic headaches. Many of the currently available neck pain treatments are invasive with associated risks and complications, particularly because of the complex anatomy. Magnetic resonance guided focused ultrasound, a novel, completely noninvasive technique, can precisely target spinal facet joints to help ameliorate neck pain, potentially transforming the current practices. The goal of this study is to develop a cervical spine-specific device and demonstrate its safety and efficacy on targeting cervical sensory fibers and the third occipital nerve. The results of these studies will provide an understanding on how to best use this technology for chronic neck pain as well as a basis for translation into human use.
3U19TW008163-10S1
DIVERSE DRUG LEAD COMPOUNDS FROM BACTERIAL SYMBIONTS IN PHILIPPINE MOLLUSKS Preclinical and Translational Research in Pain Management FIC UNIVERSITY OF UTAH HAYGOOD, MARGO GENEVIEVE Salt Lake City, UT 2018
NOFO Title: Limited Competition: International Cooperative Biodiversity Groups (U19)
NOFO Number: RFA-TW-13-001
Summary:

The Philippine Mollusk Symbiont International Cooperative Biodiversity Group harnesses the vast biodiversity of the Philippines to discover new drugs to treat bacterial infections, parasitic infections, pain, and other neurological conditions and cancer, all of which are serious health problems in both the Philippines and the United States. The Republic of the Philippines represents a unique nexus of exceptional biodiversity, dense human population with pressing societal needs, consequent urgent need for conservation, and government commitment to education and technology to harness national human and natural resources for a sustainable future. Mollusks are one of the most diverse groups of marine animals, and their associated bacteria represent an unexplored trove of chemical diversity. Researchers will use an increasing understanding of the interactions between mollusk symbionts and their hosts to discover the most novel and useful molecules. The project will document and describe Philippine mollusk biodiversity and support training and infrastructure that provide the foundation for conservation of Philippine biodiversity.
1UH3NS115118-01
Transcranial focused ultrasound for head and neck cancer pain. A pilot study Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NINDS UNIVERSITY OF VIRGINIA ELIAS, WILLIAM JEFFREY Charlottesville, VA 2019
NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018
Summary:

Head and neck cancer is particularly susceptible to nociceptive and neuropathic pains because it is dense with sensitive anatomic structures and richly innervated. Transcranial magnetic resonance imaging–guided focused ultrasound (FUS) is a new stereotactic modality capable of delivering high-intensity energy through the intact human skull with submillimeter precision. This clinical trial will target the spinothalamic and spinoreticular pain circuits by unilateral FUS mesencephalotomy, an effective procedure for cancer pain but limited by the accuracy of its era. The primary aim is to assess the safety and preliminary effectiveness in six head and neck cancer patients with opioid-resistant pain. Researchers will investigate the potential mechanism of pain relief as the mesencephalotomy target involves the confluence of the ascending and descending pain systems. Aims 2 and 3 will investigate these systems with electrophysiology specific for the spinothalamic tract and carfentenil positron emission tomography imaging that measures the brain’s endogenous opioids.
1R18EB035019-01
POWS for NOWS: Using Physiomarkers as an Objective Tool for Assessing the Withdrawing Infant Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NIBIB UNIVERSITY OF VIRGINIA SULLIVAN, BRYNNE ARCHER (contact); VESOULIS, ZACHARY ANDREW Charlottesville, VA 2023
NOFO Title: HEAL Initiative: Translational Development of Diagnostic and Therapeutic Devices (R18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-22-002
Summary:

Infants exposed to opioids during pregnancy can develop neonatal opioid withdrawal syndrome (NOWS). To date, clinicians generally use subjective evaluation to determine if an infant has NOWS, how severe the condition is, and if the infant needs treatment with or without medications. This project will evaluate whether an objective physiologic measure—continuous measurement of oxygen levels in the infant’s blood—can be used to develop a scoring system for assessing NOWS severity. The project will also develop and test a device to continuously monitor blood oxygen levels in the infants.
1U18EB029251-01
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.
1UG3NS116218-01
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.
3UH3NS116218-02S1
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.