Funded Projects

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Project # Sort descending	Project Title	Research Focus Area	Research Program	Administering IC	Institution(s)	Investigator(s)	Location(s)	Year Awarded
1R21AT012304-01	Erythrocyte Autophagy Proteins as Potential Non-Opioid Novel Targets for Pain in Sickle Cell Disease	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NCCIH	UNIVERSITY OF ILLINOIS, CHICAGO	RAMASAMY, JAGADEESH	Chicago, IL	2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: TR22-011 Summary: Sickle cell disease is an inherited blood disorder affecting about 100,000 Americans and over 20 million people worldwide. It is caused by a mutation in the gene for beta-globin that results in the characteristic sickled shape of red blood cells, life-long severe pain, and shortened lifespan. Painful episodes that require hospitalization and, in many cases, opioid treatment, are a hallmark of sickle cell disease. The source of these painful episodes remains unclear, and it is also unknown why pain severity varies so much among affected individuals. This project will identify novel, non-opioid targets to reduce sickle cell-related pain and search for biomarkers to help clinicians predict which individuals are at risk for increased pain, thereby improving health outcomes for people with sickle cell disease.
1R21DA057500-01	G Alpha Z Subunit as a Potential Therapeutic Target to Modulate Mu Opioid Receptor Pharmacology	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NIDA	UNIVERSITY OF ROCHESTER	BIDLACK, JEAN M	Rochester, NY	2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: TR22-011 Summary: Opioids affect the body by attaching to certain types of receptors that attach to G-proteins (particularly, a subtype called G-alpha). Opioids vary in their ability to provide pain relief as well as in their ability to require more drug to provide a response, known as tolerance. This project will explore the potential of various G-alpha subunits to increase or decrease opioid receptor signaling. The research findings will lay the groundwork for tailoring G-alpha related opioid effects to provide more pain relief while being less addictive.
1R21NS113335-01	Targeting the Vgf signaling system for new chronic pain treatments	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NINDS	University of Minnesota	VULCHANOVA, LYUDMILA H	Minneapolis, MN	2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R21 Clinical Trial Not Allowed) NOFO Number: RFA-NS-18-042 Summary: Chronic pain is maintained, in part, by persistent changes in sensory neurons, including a pathological increase in peptides derived from the neurosecretory protein VGF (non-acronymic). Preliminary findings show that the C-terminal VGF peptide, TLQP-62, contributes to spinal cord neuroplasticity and that TLQP-62 immunoneutralization attenuates established mechanical hypersensitivity in a traumatic nerve injury model of neuropathic pain. This project will test the hypothesis that spinal cord TLQP-62 signaling can be targeted for the development of new chronic pain treatments through immunoneutralization and/or receptor inhibition. It will pursue discovery and validation of TLQP-62-based therapeutic interventions along two parallel lines: identification of TLQP-62 receptor(s) and validation of anti-TLQP-62 antibodies as a potential biological therapeutic option for chronic neuropathic pain conditions.
1R21NS130409-01	Novel Genetically Encoded Inhibitors to Probe Functional Logic of Cav-Beta Molecular Diversity	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NINDS	COLUMBIA UNIVERSITY HEALTH SCIENCES	COLECRAFT, HENRY M	New York, NY	2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: TR22-011 Summary: High-voltage-gated calcium channels convert electrical signals into physiological responses. After a nerve injury, levels of these channels go down in some neurons in the dorsal root ganglia that communicates pain signals to and from the brain. This decline results in reduced flow of calcium that may underlie pain. This project will develop novel approaches to block these calcium channels p to further study their roles in controlling pain.
1R21NS130417-01	The Role of Lysosomal Mechano-Sensitive Ion Channel in Pain	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NINDS	INDIANA UNIVERSITY PURDUE AT INDIANAPOLIS	TAN, ZHIYONG	Indianapolis, IN	2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: TR22-011 Summary: Chronic pain severely reduces the quality of life and ability to work for millions of Americans. Because misuse of opioids for chronic pain treatment contributes to opioid addiction and opioid overdose, there is an urgent need to study novel non-opioid mechanisms, targets, and treatment strategies for chronic pain. Many ion channels control the flow of electrical signals in peripheral sensory neurons and are thus key targets for understanding and treating chronic pain. This project will conduct detailed studies to identify major ion channel-related molecular activities, targets, and treatment strategies for chronic pain. In particular, this research will explore the role of a specific ion channel (lysosomal mechanosensitive ion channel, orTmem63A) in neuropathic pain resulting from nerve injury.
1R21NS132565-01	Discovery of the Novel Targets for Post-Traumatic Headache	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	2023
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: RFA-TR-22-011 Summary: Chronic post-traumatic headache (PTH) is highly debilitating, poorly understood, and difficult to treat. This project aims to identify proteins located in the membrane of certain neurons that are critical for the development, maintenance, and/or resolution of PTH. These proteins may be targets for novel treatment approaches that are nonaddictive and have minimal side effects.
1R21NS132590-01	Structure-Function and Signaling of Glutamate Delta 1 in Pain Mechanism	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NINDS	CREIGHTON UNIVERSITY	DRAVID, SHASHANK MANOHAR	Omaha, NE	2023
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: RFA-TR-22-011 Summary: There is an urgent need to find new ways to treat chronic pain through better targeting of underlying biological processes. Research shows that flexible synapses within the amygdala brain region play a role in the progression of pain from acute to chronic, but the details are not fully understood. The receptor glutamate delta 1 helps to form and maintain synapses in the amygdala in inflammatory and neuropathic pain. This project will study how the shape and characteristics of glutamate delta 1 affect pain conditions that involve the amygdala, toward informing future development of pain medications.
1R21TR004333-01	Discovery of Novel Openers of the Understudied Human Drug Target Kir6.1	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NCATS	NEW YORK UNIVERSITY SCHOOL OF MEDICINE	CARDOZO, TIMOTHY J	New York, NY	2022
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: TR22-011 Summary: Routine treatment of pain with prescription opioid medications may evolve into opioid use disorder, addiction, and potentially overdose. New, non-opioid molecular targets for pain are needed as a key element of responding to the opioid and overdose crisis. Ion channels are molecular gateways that convert electrical signals into physiological responses, and many have been implicated in transmitting pain signals. The ion channel Kir6.1/KCNJ8 has been linked to the control of postoperative and cancer pain. Studies in animal models show that low levels of this ion channel are evident after an injury. This research will identify compounds that can open the Kir6.1/KCNJ8 channel as potential treatment strategy for pain.
1R21TR004701-01	Exploration of MBD1 as a Therapeutic Target for Chronic Pain	Preclinical and Translational Research in Pain Management	Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain	NCATS	UNIVERSITY OF MINNESOTA	STONE, LAURA S	Minneapolis, MN	2023
NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed) NOFO Number: RFA-TR-22-011 Summary: Chronic pain results in long-term changes throughout the central nervous system. These include abnormal structure and function of the frontal cortex region of the brain, which relays pain messages and also the common pain-related conditions depression, anxiety, and cognitive impairment. Peripheral nerve injury results in widespread and long-lasting changes to DNA in the frontal cortex. DNA methylation, in which chemical tags are attached to DNA, is one way the body controls the activity of genes over time. This control occurs via proteins that recognize tagged DNA, and some of these proteins do not work properly in the frontal cortex many months after nerve injury. These changes occur after nerve injury and are linked to mechanical sensitivity. This project will determine this DNA-binding protein is a good target for finding new medications for chronic pain.
1R34NS126030-01	Profiling the human gut microbiome for potential analgesic bacterial therapies	Preclinical and Translational Research in Pain Management	Development and Optimization of Non-Addictive Therapies to Treat Pain	NINDS	HOLOBIOME, INC.	STRANDWITZ, PHILIP PETER (contact); GILBERT, JACK ANTHONY	Cambridge, MA	2021
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development Initial Translational Efforts [Small Molecules and Biologics] (R34 Clinical Trial Not Allowed) NOFO Number: RFA-NS-21-016 Summary: Disruptions in make-up of the microbiome are associated with disorders characterized by chronic pain and inflammation, such as rheumatoid arthritis and fibromyalgia. The gut microbiome has immune and metabolic effects, and human gut-derived bacteria may be a source of novel, safe, and non-addictive pain treatments. However, connections between gut and pain signals, known as the “gut–pain axis,” are still poorly understood. This study aims to identify human-gut-native bacteria that i) interact with known pain targets in lab studies, ii) test their activity and analgesic/anti-inflammatory potential in an animal model, and iii) develop a computational approach to predict microbial-genetic effects on pain signals.
1R34NS126032-01	Stem cell-loaded microgels to treat discogenic low back pain	Preclinical and Translational Research in Pain Management	Development and Optimization of Non-Addictive Therapies to Treat Pain	NINDS	CEDARS-SINAI MEDICAL CENTER	SHEYN, DMITRIY	Los Angeles, CA	2021
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development Initial Translational Efforts [Small Molecules and Biologics] (R34 Clinical Trial Not Allowed) NOFO Number: RFA-NS-21-016 Summary: Pain caused by the degeneration of discs between vertebrae in the spine makes up a significant proportion of all chronic low back pain conditions. Although opioids are prescribed as treatments for this chronic condition, they often do not provide effective pain management, and currently there are no treatments that target the underlying disc disease. Notochordal cells mature into the cells that make up discs between vertebrae. Preliminary studies have shown that notochordal cells can be made from induced pluripotent stem cells, offering a potential replacement for diseased cells between discs. This study aims to develop a novel treatment for painful disc degeneration using a microgel/microtissue embedded with human notochordal cells made in the lab from induced pluripotent stem cells.
1R34NS126036-01	Synthesis of peripherally active CB1 agonists as analgesics	Preclinical and Translational Research in Pain Management	Development and Optimization of Non-Addictive Therapies to Treat Pain	NINDS	ST. LOUIS COLLEGE OF PHARMACY	MAJUMDAR, SUSRUTA (contact); DROR, RON ; GEREAU, ROBERT W	St. Louis, MO	2021
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development Initial Translational Efforts [Small Molecules and Biologics] (R34 Clinical Trial Not Allowed) NOFO Number: RFA-NS-21-016 Summary: Current medications for chronic pain are largely ineffective and rely heavily on opioids, one contributor to the nation’s opioid crisis. The endocannabinoid system that consists of cannabinoid receptors (CB1R and CB2R) and their endogenous ligands is a natural pathway in the human body and has emerged as an alternative target for developing new pain medications with few side effects. Current molecules that bind to CB1R in the brain and spinal cord have psychoactive side effects, limiting their therapeutic use for treating chronic pain. This study aims to develop new molecules to bind to CB1R tightly and selectively, are metabolically stable, and are also unable to enter the brain.
1R61NS113258-01A1	Multi-Omic Biomarkers for Neuropathic Pain Secondary to Chemotherapy	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	CLEVELAND CLINIC LERNER COM-CWRU	ROTROFF, DANIEL; FOSS, JOSEPH F; JOHNSON, KENWARD B;	Cleveland, OH	2020
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: Taxanes are among the most effective chemotherapeutic agents and are frequently used in the treatment of early stage and metastatic breast cancer. However, they are known to produce a pain condition known as Chemotherapy-Induced Peripheral Neuropathic Pain (CIPNP). CIPNP is one of the primary reasons a patient receives a limited dose of taxane. No diagnostic tool exists to identify patients that will develop CIPNP in response to taxane therapy. Biomarker signatures associated with taxane-induced neuropathic pain will be developed to: 1) identify patients at risk for developing debilitating taxane neuropathic pain before chemotherapy is initiated; and 2) to identify patients already on treatment who are at risk of developing neuropathic pain and need dosing adjustments to prevent CIPNP symptoms. This biomarker signature will be used to detect CIPNP-susceptible patients early and personalize their taxane therapy to minimize CIPNP while optimizing the therapeutic taxane dosing.
1R61NS113269-01	Validation of a novel cortical biomarker signature for pain	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	University of Maryland, Baltimore	SEMINOWICZ, DAVID	Baltimore, MD	2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: Chronic pain is a major health burden associated with immense economic and social costs. Predictive biomarkers that can identify individuals at risk of developing severe and persistent pain, which is associated with worse disability and greater reliance on opioids, would promote aggressive, early intervention that could halt the transition to chronic pain. The applicant’s team uncovered evidence of a unique cortical biomarker signature that predicts pain susceptibility (severity and duration). This biomarker signature could be capable of predicting the severity of pain experienced by an individual minutes to months in the future, as well as the duration of pain (time to recovery). Analytical validation of this biomarker will be conducted in healthy participants using a standardized model of the transition to sustained myofascial temporomandibular pain. Specifically the biomarker signature will be tested for its ability to predict an individual’s pain sensitivity, pain severity, and pain duration and will perform initial clinical validation.
1R61NS113315-01	Biomarker Signature to Predict the Persistence of Post-Traumatic Headache	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	MAYO CLINIC ARIZONA	CHONG, CATHERINE DANIELA	Scottsdale, AZ	2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: There is currently no recognized way of accurately predicting who will recover from post-traumatic headache (PTH) during the acute phase following concussion and who will go on to develop persistent post-traumatic headache (PPTH), a condition that is difficult to treat effectively. Clinical experience suggests that early treatment is most effective, before headache patterns become persistent, but treating all patients with PTH would expose some patients to unnecessary treatment. Clinicians lack the information needed to make informed treatment decisions. Therefore, the study goals are to develop a prognostic biomarker signature for PPTH using clinical data and structural and functional brain neuroimaging and to assess the predictive accuracy of an ensemble biomarker signature for the early identification of patients at high risk for PPTH. This study can be translated into clinical practice and integrated into PTH clinical trials for early identification of those individuals who are at high risk for PPTH.
1R61NS113316-01	Discovery and analytical validation of Inflammatory bio-signatures of the human pain experience	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	PROSSIN, ALAN RODNEY	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: Postoperative pain is a major contributor to the current opioid epidemic. Novel objective measures capable of personalizing pain care will enhance medical precision in prevention and treatment of postoperative pain. This project seeks to discover and validate a novel biosignature of the human pain experience, based on underlying IL-1 family cytokine activity and associated brain endogenous opioid function, that is readily quantifiable and clinically translatable to prevention and treatment of postoperative pain states. Specific aims will assess whether the novel biosignature will predict 1) experimentally induced pain during an experimental nociceptive pain challenge; 2) postoperative pain states with accuracy >75%, accounting for a wide range of variance in the human pain experience; and 3) postoperative pain states in an expanded clinically enriched sample.
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.
1R61NS113341-01	Discovery of the Biomarker Signature for Neuropathic Corneal Pain	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	Tufts Medical Center	HAMRAH, PEDRAM	Boston, MA	2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: Neuropathic corneal pain (NCP) causes patients to have severe discomfort and a compromised quality of life (QoL). The lack of signs observed by standard examination has resulted in misdiagnosis as dry eye disease (DED). An optical biopsy using laser in vivo confocal microscopy (IVCM) revealed that microneuromas (bulbs at the ends of severed nerves caused by buildup of molecular constituents) are present in NCP but not DED and may serve as a biomarker for NCP. The aims are to (1) use a database of more than 2,000 DED/NCP subjects and more than 500,000 IVCM images to confirm that the presence of microneuromas is an appropriate biomarker for NCP, (2) provide biological validation of microneuromas, (3) develop a validated artificial intelligence (AI) program for automated identification of microneuromas, and (4) establish the clinical utility of microneuromas observed by IVCM as a biomarker for NCP in a prospective, multicenter study.
1R61NS114926-01	SPRINT: Signature for Pain Recovery IN Teens	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	STANFORD UNIVERSITY	SIMONS, LAURA E	Stanford, CA	2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: Up to 5 percent of adolescents suffer from high-impact chronic musculoskeletal (MSK) pain, and only about 50 percent with chronic MSK pain who present for treatment recover. Current treatments for chronic MSK pain are suboptimal and have been tied to the opioid crisis. Discovery of robust markers of the recovery versus persistence of pain and disability is essential to develop more resourceful and patient-specific treatment strategies, requiring measurements across multiple dimensions in the same patient cohort in combination with a suitable computational analysis pipeline. Preliminary data has implicated novel candidates for neuroimaging, immune, quantitative sensory, and psychological markers for discovery. In addition, a standardized specimen collection, processing, storage, and distribution system is in place, along with expertise in machine learning approaches to extract reliable and prognostic bio-signatures from a large and complex data set. This project will facilitate risk stratification and a resourceful selection of patients who are likely to respond to current multidisciplinary pain treatment approaches.
1R61NS114954-01	The Inflammatory Index as a Biomarker for Pain in Patients with Sickle Cell Disease	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	MEDICAL COLLEGE OF WISCONSIN	BRANDOW, AMANDA M	Milwaukee, WI	2019
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: Debilitating pain is the most common complication of sickle cell disease (SCD), but there is significant variability in pain expression in these patients. Currently, there is no plasma biomarker that can prognosticate which patients are likely to experience pain. The overall goal of this proposed research is to develop a biomarker that prognosticates the clinical expression of pain in SCD. Project aims are to (1) derive the inflammatory index for pain by identifying inflammatory and immune regulatory gene probe sets that will distinguish healthy controls, patients with SCD in baseline health, and patients with SCD in acute pain and (2) determine whether co-expressed genes from patients with SCD correlate with clinical pain data. Subsequent aims are to (1) determine the clinically meaningful changes of the index in patients with SCD and (2) investigate the preliminary clinical validity of the index as a prognostic biomarker for pain in patients with SCD.
1R61NS118651-01A1	Prognostic Biomarkers for High-Impact Chronic Pain: Development and Validation	Preclinical and Translational Research in Pain Management	Discovery and Validation of Biomarkers, Endpoints, and Signatures for Pain Conditions	NINDS	STANFORD UNIVERSITY	MACKEY, SEAN C	Redwood City, CA	2020
NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional) NOFO Number: RFA-NS-18-041 Summary: Multidisciplinary chronic pain treatments show incomplete recovery at the population level because of significant heterogeneity on the individual level in the high impact chronic pain population. Subgroups of individuals either completely respond, do not change, or even worsen following pain management. Therefore, diagnostic biomarker signatures are needed to differentiate high impact chronic pain from low impact chronic pain. This study aims to develop prognostic biomarkers to predict the disease trajectory for individuals with musculoskeletal high-impact chronic pain. These biomarker signatures will integrate central nervous system (CNS), multi-?omic?, sensory, functional, psychosocial, and demographic domains into detection algorithms. Biomarker signatures from the proposed research are intended to facilitate risk and treatment stratification for clinical trial design and to facilitate treatment decisions in clinical practice for patients with musculoskeletal chronic pain.
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.
1R61NS126029-01A1	Inhibiting RIPK1 with Necrostatin-1 for Safe and Effective Pain Treatment	Preclinical and Translational Research in Pain Management	Development and Optimization of Non-Addictive Therapies to Treat Pain	NINDS	Massachusetts General Hospital	SHEN, SHIQIAN (contact); HOULE, TIMOTHY T; WANG, CHANGNING ; ZHANG, CAN MARTIN	Boston, MA	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: Recent studies have reported that neuropathic pain involves changes in the central nervous system that are linked to necroptosis (programmed necrotic cell death) and release of cellular components that create neuroinflammation. Necroptosis is a type of necrotic cell death affected by the protein receptor-interacting serine/threonine-protein kinase 1 (RIPK1 or RIP1). Preliminary studies also indicate that pain increases levels of RIPK1 in key brain regions implicated in pain processing. This project aims to further validate RIPK1 as a target for neuropathic pain using a newly developed positron emission tomography imaging approach. The work will pave the way for new brain-penetrant RIPK1 inhibitors as a safe, effective, and nonaddictive treatment approach for neuropathic pain.
1R61NS127271-01A1	Planning Study for the Development of Sigma 2 Ligands as Analgesics	Preclinical and Translational Research in Pain Management	Development and Optimization of Non-Addictive Therapies to Treat Pain	NINDS	UNIVERSITY OF KENTUCKY	TIDGEWELL, KEVIN JOSEPH (contact); KOLBER, BENEDICT J	Lexington, KY	2023
NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed) NOFO Number: RFA-NS-21-029 Summary: Natural products, which are substances found in nature and made by living organisms, have been used in the past as good sources for developing new medications. Natural products isolated from marine bacteria that attach to the pain-signaling protein sigma-2 receptor (also known as transmembrane protein 97 [TMEM97]), may serve as a starting point to create new, non-opioid pain medications. This project will use chemistry and biology approaches to refine such natural products as a treatment for neuropathic pain.
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.