Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1U24AR076730-01
Back Pain Consortium (BACPAC) Research Program Data Integration, Algorithm Development and Operations Management Center Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS UNIV OF NORTH CAROLINA CHAPEL HILL ANSTROM, KEVIN J (contact); IVANOVA, ANASTASIA ; LAVANGE, LISA Chapel Hill, NC 2019
NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Data Integration, Algorithm Development and Operations Management Center (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-AR-19-027
Summary:

The BACPAC Research Program’s Data Integration, Algorithm Development, and Operations Management Center (DAC) will bring cohesion to research performed by the participating Mechanistic Research Centers, Technology Research Sites, and Phase 2 Clinical Trials Centers. DAC Investigators will share their vision and provide scientific leadership and organizational support to the BACPAC Consortium. The research plan consists of supporting design and conduct of clinical trials with precision interventions that focus on identifying the best treatments for individual patients. The DAC will enhance collaboration and research progress with experienced leadership, innovative design and analysis methodologies, comprehensive research operations support, a state-of-the-art data management and integration system, and superior administrative support. This integrated structure will set the stage for technology assessments, solicitation of patient input and utilities, and the evaluation of high-impact interventions through the innovative design and sound execution of clinical trials, leading to effective personalized treatment approaches for patients with chronic lower back pain.
1R01NS118504-01
Targeting GPCRs in Amygdalar and Cortical Neural Ensembles to Treat Pain Aversion Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIV OF NORTH CAROLINA CHAPEL HILL SCHERRER, GREGORY Chapel Hill, NC 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:

There is a distinct neural ensemble in the brain that encodes the negative affective valence of pain. This project will identify novel targets to treat pain by determining the molecular identity of these BLA nociceptive cells via in situ hybridization and single cell RNAsequencing (scRNA-seq). Resolving the molecular identity of these ACC nociceptive cells will also reveal new targets to treat pain affect. To achieve these results the project will catalog candidate Gi/o-GPCR targets in BLA and ACC, test their utility to treat pain, and verify these new targets have no effect in the brain?s reward and breathing circuitry. The experiments in this project will also evaluate each target for abuse potential and effects on breathing by using behavioral assays for reward processing and whole-body plethysmography, respectively. To evaluate whether our results in rodents are likely to translate clinically, there will be an analysis of expression patterns of these drug targets in human tissue using in situ hybridization.
5R01NS102432-02
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.
1R01NS116694-01
Validation of Spinal Neurotensin Receptor 2 as an Analgesic Target Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF ARIZONA PATWARDHAN, AMOL M Tuscon, AZ 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:

Epidural/spinal administration of analgesics such as opioids, ziconotide and local anesthetics have profound efficacy in some of the most intractable pain conditions such as severe neuropathic pain after failed back surgery, cancer pain and post-operative pain after major abdominal/thoracic surgeries. Contulakin G (CGX) is a snail venom derived peptide that has homology with mammalian neurotensin and was shown to be safe in humans in preliminary studies. A small pilot study demonstrated CGX?s analgesic effect in some patients with spinal cord injury-associated pain. Preliminary findings from mechanistic studies in rodents identified neurotensin receptor 2 (NTSR2) as the mediator for analgesic effects of CGX. This project aims to validate spinal NTSR2 as an analgesic target utilizing three species (rat, mice and human), and two pain models (neuropathic pain and post-surgical pain). The project will utilize pharmacological and gene editing tools such as CRISPR-Cas9 and will include assessment of both sensory and affective measures of pain. A two-site parallel confirmation study is designed based on multisite clinical trials to further authenticate spinal NTSR2 as an analgesic target. Successful completion of this project could lead to the development of a non-opioid spinal analgesic that has high translational potential.
1R61NS126026-01A1
Antagonists of CRMP2 Phosphorylation for Chemotherapy-Induced Peripheral Neuropathy Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF ARIZONA KHANNA, RAJESH Tucson, Arizona 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:

A more thorough understanding of neuropathic pain is critical for developing new target-specific medications. Researchers know that peripheral nerve injury changes various cell processes that affect two ion channels linked with chronic pain. Preliminary studies indicate that molecular changes known as phosphorylation to the collapsin response mediator protein 2 (CRMP2), one of five intracellular phosphoproteins, promotes abnormal excitability in the brain region that contributes to neuropathic pain. This project aims to develop small molecule inhibitors of CRMP2 phosphorylation as potential therapeutics for pain.
1R01NS120663-01A1
Genetic and Pharmacological Validation of CRMP2 Phosphorylation 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 UNIVERSITY OF ARIZONA KHANNA, RAJESH Tucson, AZ 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:

Peripheral nerve injury-induced upregulation of three axonal guidance phosphoproteins correlates with the development of neuropathic pain through an unidentified mechanism: 1) collapsin response mediator protein 2 (CRMP2); 2) the N-type voltage-gated calcium (CaV2.2); 3) the NaV1.7 voltage-gated sodium channel. Injury induced phosphorylated-CRMP2/CaV2.2 and phosphorylated-CRMP2/NaV1.7 upregulation in the sensory pathway may promote abnormal excitatory synaptic transmission in spinal cord that leads to neuropathic pain states. This project will validate CRMP2 phosphorylation as a novel target in neuropathic pain using innovative tools. Examples include a genetic approach (crmp2S522A) in mice as well as a non-opioid pharmacological approach (a novel CRMP2-phsphorylation targeting compound). Demonstrating that inhibition of CRMP2 phosphorylation reverses or prevents neuropathic pain will promote the discovery and validation of a novel therapeutic target (CRMP2-phosphorylation) to facilitate the development of novel pain therapeutics.
1UG3NS114956-01
Optimization of non-addictive biologics to target sodium channels involved in pain signaling Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS UNIVERSITY OF CALIFORNIA AT DAVIS YAROV-YAROVOY, VLADIMIR M Davis, CA 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:

Pain signals originate predominantly in a subset of peripheral sensory neurons that harbor a distinct subset of voltage-gated sodium (NaV) channels; however, current NaV channel blockers, such as local anesthetics, are non-selective and also block NaV channels vital for function of the heart, muscle, and central nervous system. Genetic studies have identified human NaV1.7, NaV1.8, and NaV1.9 channel subtypes as key players in pain signaling and as major contributors to action potential generation in peripheral neurons. ProTx-II is a highly potent and moderately selective peptide toxin that inhibits human NaV1.7 activation. This study will optimize ProTx-II selectivity, potency, and stability by exploiting the new structures of ProTx-II—human NaV1.7 channel complexes, advances in rational peptide optimization, and rigorous potency and efficacy screens to generate high-affinity, selective inhibitors of human NaV1.7, NaV1.8, and NaV1.9 channels that can define a new class of biologics to treat pain.
1R61AT012187-01
Total-Body PET for Assessing Myofascial Pain Clinical Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCCIH UNIVERSITY OF CALIFORNIA AT DAVIS CHAUDHARI, ABHIJIT J (contact); NARDO, LORENZO Davis, CA 2022
NOFO Title: HEAL Initiative: Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management
NOFO Number: RFA-AT-22-003
Summary:

Myofascial pain syndrome is a prevalent and debilitating condition and can aggravate other conditions such as sickle cell disease. This project will use total body imaging using positron emission tomography/computed tomography (TB-PET/CT) to identify and monitor this pain syndrome and potential treatments over time. The research will use TB-PET/CT to assess myofascial tissue effects of chronic low back pain and sickle cell disease pain. The first phase of the project will assess health changes observed by TB-PET/CT imaging in painful and non-painful myofascial tissues compared to healthy myofascial tissue. The second phase of the research will be a randomized, controlled longitudinal interventional study to evaluate the effectiveness of acupuncture on myofascial pain syndrome, using TB-PET/CT imaging to assess changes.
1UG3TR003148-01
Multi-organ-on-chip device for modeling opioid reinforcement and withdrawal, and the negative affective component of pain: a therapeutic screening tool. Preclinical and Translational Research in Pain Management Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS UNIVERSITY OF CALIFORNIA LOS ANGELES MAIDMENT, NIGEL T (contact); ASHAMMAKHI, NUREDDIN ; SEIDLITS, STEPHANIE KRISTIN; SVENDSEN, CLIVE NIELS Los Angeles, CA 2019
NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003
Summary:

Researchers will develop multi-organ, microphysiological systems (MPSs) based on human induced pluripotent stem cell-derived midbrain-fated dopamine (DA)/gamma-aminobutyric acid neurons on a three-dimensional platform that incorporates microglia, blood–brain barrier (BBB), and liver metabolism. RNA sequencing and metabolomics analyses will complement the primary DA release measure to identify novel mechanisms contributing to chronic opioid-induced plasticity in DA responsiveness. The chronic pain-relevant aspect of the model will be realized by examination of aversive kappa-mediated opioid effects on DA transmission in addition to commonly abused mu opioid receptor agonists, and by incorporation of inflammatory-mediating microglia. Incorporation of BBB and liver metabolism modules into the microphysiologic system platform will permit screening of drugs. Throughput will be increased by integration of online sensors for online detection of DA and other analytes. Researchers will use a curated set of 100 chemical genomics probes.
1UH3NS113661-01
Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain Preclinical and Translational Research in Pain Management Translating Discoveries into Effective Devices to Treat Pain NINDS UNIVERSITY OF CALIFORNIA LOS ANGELES BARI, AUSAF (contact); POURATIAN, NADER Los Angeles, CA 2019
NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018
Summary:

This study aims to address critical gaps and unmet therapeutic needs of chronic low back pain (CLBP) patients using a next-generation deep brain stimulation (DBS) device with directional steering capability to engage networks known to mediate the affective component of CLBP. Researchers will utilize patient-specific probabilistic tractography to target the subgenual cingulate cortex (SCC) to engage the major fiber pathways mediating the affective component of chronic pain. The objective is to conduct an exploratory first-in-human clinical trial of SCC DBS for treatment of medically refractory CLBP. The research team aims to: (1) assess the preliminary efficacy of DBS of SCC in treatment of medically refractory CLBP; (2) demonstrate the safety and feasibility of SCC DBS for CLBP; and (3) develop diffusion tensor imaging–based blueprints of response to SCC DBS for CLBP.
1R61NS127285-01
Development of Therapeutic Antibodies to Target Sodium Channels Involved in Pain Signaling Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS University of California, Davis YAROV-YAROVOY, VLADIMIR M (contact); TRIMMER, JAMES S Davis, CA 2022
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: NS21-029
Summary:

Voltage-gated sodium channels such as Nav1.7, Nav1.8, and Nav1.9 transmit pain signals in nerve fibers and are molecular targets for pain therapy. While Nav channels have been validated as pharmacological targets for the treatment of pain, available therapies are limited due to incomplete efficacy and significant side effects. Taking advantage of recent advances in structural biology and computational-based protein design, this project aims to develop antibodies to attach to Nav channels and freeze them in an inactive state. These antibodies can then be further developed as novel treatments for chronic pain.
1R61MH132249-01
Latinx Children and Surgery Clinical Research in Pain Management Advancing Health Equity in Pain Management NIMH University of California, Irvine KAIN, ZEEV Irvine, CA 2022
NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

Both pain experience and treatment response are determined by a variety of factors, including race and ethnicity. Inequities in access to healthcare and pain treatment affect patients from minority populations, such as Hispanic/Latino populations of all age groups. This study will develop and test an online intervention—Web-based Tailored Intervention for Preparation of Parents and Children for Outpatient Surgery (L-WebTIPS)—tailored for Latino families of children having outpatient surgeries. The intervention aims to lower child and family anxiety before surgery as well as to reduce post-surgical pain by enhancing parent self-efficacy and behavioral pain coping strategies. After an exploratory phase to assess usability and acceptability of the intervention, the study will evaluate the impact of L-WebTIPS on child pre-surgery anxiety and post-surgery pain as well assess other child and parent outcomes.
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.
1U24NS115714-01
California Clinical and Translational Pain Research Consortium Clinical Research in Pain Management Early Phase Pain Investigation Clinical Network (EPPIC-Net) NINDS UNIVERSITY OF CALIFORNIA, SAN DIEGO WALLACE, MARK S San Diego, CA 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
Summary:

The California Clinical and Translational Pain Research Consortium (CCTPRC) consists of four University of California academic medical centers with considerable experience in pain management clinical trials, phenotyping, and biomarker validation. The network will leverage solid existing Clinical and Translational Science Award (CTSA) resources to make clinical trial execution efficient and rapid. The hub will be located at the University of California, San Diego, with spokes located on the other three campuses to provide maximum flexibility, ready to accommodate studies in a variety of pain conditions and provide successful recruitment and high-quality data collection.
1UH2AR076719-01
Novel imaging of endplate biomarkers in chronic low back pain Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS UNIVERSITY OF CALIFORNIA, SAN FRANCISCO FIELDS, AARON J (contact); KRUG, ROLAND San Francisco, CA 2019
NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Technology Research Sites (UH2/UH3 Clinical Trial Optional)
NOFO Number: RFA-AR-19-028
Summary:

This project will examine the association between end plate pathology and chronic low back pain (cLBP) and improve patient selection by developing and translating new imaging tools, technologies, and/or methods (iTTM) that provide accurate, noninvasive measures of end plate pathologies. A search for clinically relevant biomarkers of end plate pathology will focus on novel imaging measures of end plate bone marrow lesion (BML) severity with IDEAL MRI and cartilage endplate (CEP) fibrosis/damage with UTE MRI, assess interactions with paraspinal muscles, and identify metrics that associate with pain, disability, and degeneration. The research will refine imaging and post-processing methodologies by leveraging and expanding existing cross-sectional cohorts and then deploy and validate the new end plate iTTM to other BACPAC sites to test the most promising metrics’ clinical utility. These studies will provide validated iTTM that are useful for addressing the end plates pathology’s role in cLBP, identifying sub-phenotypes, discovering pain mechanisms, uncovering treatment targets, and selecting patients.
1U19AR076737-01
UCSF Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS UNIVERSITY OF CALIFORNIA, SAN FRANCISCO LOTZ, JEFFREY C San Francisco, CA 2019
NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program: Mechanistic Research Centers (U19 Clinical Trial Optional)
NOFO Number: RFA-AR-19-026
Summary:

The UCSF Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain (UCSF REACH) is an interdisciplinary consortium of basic and clinical scientists dedicated to understanding and clarifying the biopsychosocial mechanisms of chronic low back pain (cLBP). The goal of REACH is to define cLBP phenotypes and pain mechanisms that can lead to effective, personalized treatments for patients across the population. UCSF REACH has six cores that will support a single research project that is focused on the challenge of developing validated and adoptable tools that enable comprehensive yet routine clinical assessment and treatment of cLBP patients. Overall, the object of REACH is to make optimum use of all available resources to catalyze discovery and translation of novel diagnostics and therapeutics that improve outcomes of cLBP patients.
1R61NS129050-01
Integrating Nonpharmacologic Strategies for Pain with Inclusion, Respect, and Equity (INSPIRE): Tailored Digital Tools, Telehealth Coaching, and Primary Care Coordination Clinical Research in Pain Management Advancing Health Equity in Pain Management NINDS University of California, San Francisco SATTERFIELD, JASON M San Francisco, CA 2022
NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

There is a need to improve access to treatments and address the stigma, bias, and mistrust that harm and isolate people with chronic pain, especially those from ethnic and racial minority populations. The Integrating Nonpharmacologic Strategies for Pain with Inclusion, Respect, and Equity (INSPIRE) Chronic Pain (CP) intervention blends cognitive-behavioral therapy, physical therapy, mindfulness, and pain education, and is delivered by a trilingual mobile app and supported by a telehealth pain coach who coordinates with doctors. The coach will collect and summarize patient reports on pain, depression, anxiety, substance use, and social factors, and share them with healthcare providers. In this project, researchers will create the digital tool and coaching protocol, develop educational and implementation strategies for healthcare providers, and conduct a pilot test. They will then perform a randomized clinical trial to compare INSPIRE to current treatment, analyze its effects, and evaluate outcomes.
1R61MD018333-01
Group-Based Integrative Pain Management: A Multi-Level Approach to Address Intersectional Stigma and Social Isolation in Diverse Primary Care Safety Net Patients with Chronic Pain Clinical Research in Pain Management Advancing Health Equity in Pain Management NIMHD University of California, San Francisco CHAO, MARIA San Francisco, CA 2022
NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

Many barriers exist in primary care offices where socioeconomically disadvantaged patients are most often treated. This project seeks to address chronic pain disparities that affect racially diverse, socioeconomically disadvantaged individuals. The study aims to optimize multimodal pain management in primary care clinics for low-income populations. This study includes two group-based models: integrative group medical visits and group acupuncture. These two interventions will be compared to typical treatment to measure both pain interference and social isolation. National experts and patient stakeholders will refine and optimize the design of the study with English- or Spanish-speaking patients with chronic pain in two primary care clinics for low-income populations.
1UH2AR076724-01
Technology Research Site for Advanced, Faster Quantitative Imaging for BACPAC Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS UNIVERSITY OF CALIFORNIA, SAN FRANCISCO MAJUMDAR, SHARMILA San Francisco, CA 2019
NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Technology Research Sites (UH2/UH3 Clinical Trial Optional)
NOFO Number: RFA-AR-19-028
Summary:

Despite the significance of spine disorders, there are few reliable methods to determine appropriate patient care and evaluate intervention effectiveness. The research and tool development take the critical next step in the clinical translation of faster, quantitative magnetic resonance imaging (MR) of patients with lower back pain. The multidisciplinary Technology Research Site (Tech Site) of BACPAC will develop Phase IV (i.e., technology optimization) technologies and/or methods (TTMs) to leverage two key technical advancements: development of machine learning-based, faster MR acquisition methods and machine learning for image segmentation and extraction of objective disease related features from images. The team will develop, validate, and deploy end-to-end deep learning-based technologies (TTMs) for accelerated image reconstruction, tissue segmentation, and detection of spinal degeneration to facilitate automated, robust assessment of structure-function relationships between spine characteristics, neurocognitive pain response, and patient-reported outcomes.
3UH3AR076724-03S1
Technology Research Site for Advanced, Faster Quantitative Imaging for BACPAC Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS University of California, San Francisco MAJUMDAR, SHARMILA San Francisco, CA 2021
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
Summary:

Chronic low back pain affects millions of Americans and is difficult to treat. Currently, there are no reliable methods to determine the best treatment options for patients, or to objectively evaluate the effectiveness of various interventions. This research will develop an imaging technology that uses machine learning to make automated assessments of spine characteristics, pain response, and patient-reported outcomes in people with chronic low back pain. This award will be used to recruit and support two postdoctoral fellows from populations underrepresented in biomedicine. The research will focus on whether use of the imaging tool helps clarify clinical diagnoses, as measured by the level of agreement between radiologists before and after using the tool.
3U19AR076737-01S1
UCSF Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS UNIVERSITY OF CALIFORNIA, SAN FRANCISCO LOTZ, JEFFREY C. San Francisco, CA 2020
NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Promote Training in Clinical Research on Pain (Admin Supp ? Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-044
Summary:

Chronic low back pain is difficult to diagnose and treat effectively in part, because of the interplay of biophysical and psychosocial influences that complicate the relationship between impairment, disability, and pain. Psychological factors such as fear of movement and catastrophyzing can lead to compensatory movement patterns that affect movement biomechanics and paraspinal structure and function, driving further impairment, disrupting the balance between passive and active spine stabilizers, and reinforcing the patient?s perceived disability status. This study will support research to determine how psychological factors, spinal pathology, and perception of pain severity and disability status influence compensatory movement strategies, how movement biomechanics, psychological factors, and pain mechanisms relate to paraspinal muscle quality, and their relative changes during treatment. The supplement will provide training opportunities for skills in clinical pain management research.
1UH3NS115631-01
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.
3R01AT010757-02S1
The study of Gpr149 in nociception and the peripheral action of minor cannabinoids Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NCCIH UNIVERSITY OF CALIFORNIA, SAN FRANCISCO HELLMAN, JUDITH San Francisco, 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:

The cannabis plant contains many active compounds known collectively as cannabinoids that have been shown to possess analgesic and anti-inflammatory properties. These compounds exert their biological activity, in part, through the cannabinoid receptor. The cannabinoid receptor is a member of a class of proteins known as G-protein coupled receptors (GPCRs). This study will test whether a GPCR with unknown biological function, called Gpr149, has a role in the activity of cannabinoids. The study will identify and characterize Gpr149 expression in mouse cells, and deeply characterize the action of minor cannabinoids, endocannabinoids and products of inflammation to modulate Gpr149. This research will provide insight into the analgesic and anti-inflammatory action of minor cannabinoids and into the role of Gpr149 in nociception and the sensitization of nociceptors to inflammatory mediators.
3U24DK116214-02S1
ILLUMINATING DRUGGABLE DARK MATTER Preclinical and Translational Research in Pain Management NIDDK UNIVERSITY OF CALIFORNIA, SAN FRANCISCO MCMANUS, MICHAEL T; JAN, LILY Y San Francisco, 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:

The goal of this project is to generate data and reagents that help uncover critical functions of the poorly characterized members of ion channels. It focuses on co-perturbation of ion channel genes and their interacting genetic components as opposed to singly altering ion channel genes in mouse models. This approach will validate our proteomics approaches in the most definitive manner: in vivo. We see in vivo exploration as an essential step to evaluate ion channel function. Our major aims include mapping ion channel interactions and complexes using a high-throughput proteomics platform at UCSF. These data will be interrogated using integrative approaches established by the Monarch Initiative, where biochemical interactions will be validated and prioritized for further study. Another major aim is function-centric: We use mouse models for elucidation of human disease mechanisms, where we embrace a genetic interaction scheme to uncover ion channel redundancy and polygenic effects.
3U19AR076737-01S2
REACH Participant Diversity Program Clinical Research in Pain Management Back Pain Consortium Research Program NIAMS UNIVERSITY OF CALIFORNIA, SAN FRANCISCO LOTZ, JEFFREY C San Francisco, 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:

The University of California, San Francisco, as part of the Back Pain Consortium (BACPAC) Research Program, has established a Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain (REACH). The main goal of REACH is to define different subtypes (phenotypes) of chronic low back pain as well as to identify underlying pain mechanisms that can lead to effective, personalized treatments for patients across all population subgroups. To achieve this goal, REACH is, or will be, participating in several clinical trials, and it is imperative that the patients participating in these trials reflect the diversity of the U.S. population. Therefore, this project seeks to adapt methods that have successfully improved minority participation in other settings as well as to develop and deploy digital strategies that can promote recruitment and engagement of patients from marginalized populations.