Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
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.
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.
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.
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.
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.
1U19NS130607-01
INTERCEPT: Integrated Research Center for Human Pain Tissues Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS WASHINGTON UNIVERSITY GEREAU, ROBERT W Saint Louis, MO 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will use a variety of state-of-the-art technologies to generate a comprehensive  gene expression map of human peripheral nerves. The research will enhance understanding about genes involved in various painful conditions associated with nerve damage (neuropathies) resulting from injury or disease. This research will analyze DNA sequences of individual neuronal and non-neuronal cells in human nerve cells (from individuals with and without pain located outside the spinal cord that are involved in pain signal transmission. The findings, together with other imaging and computational approaches, will be used to generate a spatial atlas of the human dorsal root ganglia – a key hub for pain communication between the brain and spinal cord.
1RF1NS130481-01
Immune Modulating Therapies to Treat Complex Regional Pain Syndrome Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS DREXEL UNIVERSITY AJIT, SEENA Philadelphia, PA 2022
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Complex regional pain syndrome is a difficult-to-treat chronic condition that causes excess and prolonged pain and inflammation after injury to an arm or leg and includes damage to skin of affected limbs. Although it is known that aberrant immune system function plays a role in this condition, the details remain unclear about how this occurs – in particular, through the adaptive immune system that relies on specialized immune cells and antibodies to protect the body from harm.  This project will study the role of certain immune cells (T cells) that circulate throughout the body or reside in bone using both rat or human bone samples from patients with complex regional pain syndrome.
1R01HD110922-01
CMG2 as a Target for Safe and Effective Treatment of Endometriosis-Associated Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NICHD BOSTON CHILDREN'S HOSPITAL ROGERS, MICHAEL SEAN Boston, MA 2022
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Endometriosis is an often-painful disorder in which uterine tissue grows outside the uterus. Treatment of endometriosis-associated pain involves use of opioids in many women. This project aims to study a culprit gene thought to be involved with the disorder (capillary morphogenesis gene or CMG2) as a target for new, nonopioid pain medications. The research will also clarify how CMG2 s affects endometriosis-associated pain to test the effects of new medications for endometriosis 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 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will identify molecular characteristics of human sensory neurons and non-neuronal cells from the human dorsal root ganglia. This structure located outside the spinal cord is integrally involved in communicating pain signals to and from the brain. The research will use molecular approaches to characterize tissues obtained from organ donors and in patients who experience chronic pain. The findings will also help generate a connectivity map, or “connectome,” of nerve cell connections between the dorsal root ganglia of the spinal cord and the brain.
1R01DE032501-01
Targeting HB-EGF and Trigeminal EGFR for Oral Cancer Pain and Opioid Tolerance Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDCR NEW YORK UNIVERSITY YE, YI New York, NY 2022
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Oral cancers are painful and often require use of opioid medications to manage pain. However, the effectiveness of opioids often wanes quickly, and many patients require higher doses because they develop tolerance to these medications. This project will study the potential value of blocking epidermal growth-factor receptors interacting with peripheral nerves to treat oral cancer pain. The findings will advance understanding of the molecular mechanisms underlying oral cancer pain and provide a rationale for repurposing epidermal growth-factor receptor blockers, which is already approved for head and neck cancer treatment for treating oral cancer and associated pain.
1R01DK135076-01
PNPase Inhibition as an Effective Treatment for Chronic Bladder Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDDK UNIVERSITY OF PITTSBURGH AT PITTSBURGH BIRDER, LORI A (contact); JACKSON, EDWIN KERRY Pittsburgh, PA 2022
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Chronic visceral pain disorders, such as interstitial cystitis/bladder pain syndrome, are among the most difficult types of pain to treat. This project will conduct a detailed analysis of an enzyme thought to be involved with the disorder (purine nucleoside phosphorylase, or PNPase) as a target for new nonopioid pain medications to treat interstitial cystitis/bladder pain syndrome. The research will lay the groundwork for developing targeted treatments for visceral pain disorders.
1U19NS130617-01
Harvard PRECISION Human Pain Center Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS BRIGHAM AND WOMEN'S HOSPITAL RENTHAL, WILLIAM RUSSELL (contact); WOOLF, CLIFFORD J Boston, MA 2022
NOFO Title: HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will use state-of-the-art technologies to analyze individual cells to characterize how human pain receptors communicate pain between the human dorsal root ganglia and the brain – including how the signals vary across diverse populations. This research will generate useful, high-quality human data about pain for further analysis and re-use by other scientific teams, toward identifying and prioritizing novel therapeutic targets for pain.
1R01DK134989-01
Signal Integration by Specialized Mesenchyme in Urothelial Homeostasis and Interstitial Cystitis/Bladder Pain Syndrome Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDDK STANFORD UNIVERSITY BEACHY, PHILIP A Redwood City, CA 2022
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Interstitial cystitis/bladder pain syndrome is a debilitating disease affecting many women. Opioid-based pain management is a common feature of current treatment approaches but is associated with the risk of addiction. The causes of this disorder remain unknown, and no effective treatments are available. This project will provide new insights using genetic, medication-based and other approaches in a mouse model, along with single-cell gene expression studies conducted with cells from mice and human patients who have this condition. The analyses will help provide targeted, safe, and effective treatment approaches for individuals with interstitial cystitis/bladder pain syndrome.
3R01DE029951-01S1
Targeting Endosomal Receptors for Treatment of Chronic Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDCR NEW YORK UNIVERSITY BUNNETT, NIGEL W New York, NY 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:

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins and play important roles in inflammation and pain. GPCR signaling is fast and temporary, making it hard to measure in clinical studies of potential drugs to interfere with the signaling. This research is using selectively designed nanoparticles to stimulate or block GPCRs toward identifying new treatments for oral cancer pain. This award will use a new nanoformulation approach to understand how nanoparticles affect nerve function by i) testing the effects of continuous release of a GPCR inhibitor in an oral cancer microenvironment and ii) investigating the influence of various physicochemical characteristics of nanoparticles on nerve function in an oral cancer microenvironment.
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.
3R37DA020686-13S1
Role for Tas2Rs in opioid addiction Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDA ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI KENNY, PAUL J. New York, NY 2020
NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

Opioids and other addictive substances have powerful rewarding properties that drive the development of addiction. They also have aversive properties that motivate their avoidance and protect against addiction. This project will explore the role of Type 2 Taste Receptor proteins (Tas2Rs or T2Rs) in regulating the aversive properties of opioids, potentially establishing an entirely new class of receptors that can be targeted for the development of novel addiction therapeutics.
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.
1RF1AG068997-01
Subchondral Bone Cavities in Osteoarthritis Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS JOHNS HOPKINS UNIVERSITY CAO, XU; GUAN, YUN Baltimore, MD 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:

A key marker of inflammation in Osteoarthritis (OA) is accompanied by significantly increased sensory innervation within the diseased joint. This study aims to validate the hypothesis that defective bone resorbing cells are responsible for the enlarged bone cavity, giving rise to the inflammatory marker causing further increases in levels sensory innervation and resulting in increased OA pain perception.
3R01NS113257-01S1
Isolation of GPR160 for biochemical analysis of the activation mechanism and development of a high throughput screening assay to identify small molecule inhibitors Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS SAINT LOUIS UNIVERSITY SALVEMINI, DANIELA Saint Louis, MO 2020
NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

Neuropathic pain conditions are difficult to treat, and novel non-narcotic analgesics are desperately needed. The G protein-coupled receptor 160 (GPR160) has emerged as a novel target for analgesic development, as GPR160 in the spinal cord may play a role in the transition from acute to chronic pain. Cocaine- and Amphetamine-Regulated transcript peptide (CARTp) was identified as a ligand for GPR160. Blocking endogenous CARTp signaling in the spinal cord attenuates neuropathic pain, whereas intrathecal injection of CARTp evokes painful hypersensitivity in rodents through GPR160-dependent extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding pathways (CREB). This project will isolate and biochemically characterize GPR160 and establish methods for biochemical characterization of GPR160 interaction with CARTp activator. Researchers will miniaturize and optimize biochemical assay and scale up protein production for future high throughput biochemical screening to identify potent inhibitors of GPR160 activation. These studies are critical for defining the molecular mechanism of CARTp/GPR160 interactions and initiating large-scale screens for new inhibitors to develop novel therapeutics.
1R01CA249939-01
Identification of Novel Targets for the Treatment of Chemotherapy-Induced Painful Peripheral Neuropathy Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS UNIVERSITY OF MARYLAND BALTIMORE MELEMEDJIAN, OHANNES KEVORK Baltimore, MD 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:

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN accounts for significant dose reductions and/or discontinuation of these life-saving treatments. Unfortunately CIPN can also persist in cancer-survivors, adversely affecting their quality of life. CIPN is not well-managed with existing pain therapeutics. Recent preliminary findings suggest that the transcription factor hypoxia-inducible factor alpha (HIF1A) is the target for the chemotherapeutic bortezomib, a proteasome inhibitor. This project will test the hypothesis that bortezomib chemotherapy-induced expression of HIF1A, PDHK1 and LDHA constitute an altered metabolic state known as aerobic glycolysis (AG) that leads to the initiation and maintenance of peripheral neuropathy and pain using a novel tumor-bearing animal model of CIPN. This project aims to validate HIF1A as a therapeutic target for the prevention of CIPN, as well as validate PDHK1 and LDHA as non-opioid therapeutic targets for chronic or established CIPN in animal models.
3R35NS105092-03S1
The biophysics of skin-neuron sensory tactile organs and their sensitivity to mechanical and chemical stress Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS STANFORD UNIVERSITY GOODMAN, MIRIAM B Palo Alto, CA 2020
NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

This project will establish a rapid research pipeline for linking plant-derived compounds to nociception (pain) and to G Protein-Coupled Receptors (GPCRs) and ion channels in the druggable human genome. As more than 80% of these membrane proteins are conserved in the C. elegans nematodes, the study will screen for compounds and genes affecting nociception as well as to identify novel ligand-receptor pairs using this model organism. The study will test which understudied GPCRs and ion channels are involved in nociception as well as attraction or repulsion behaviors. This research has the potential to reveal novel ligand-receptor pairs that could serve as new entry points for improved or alternative pain treatments.
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.
1R01NS117340-01
B Lymphocyte-Mediated Autoimmunity in Pain After Trauma Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS PALO ALTO VETERANS INSTIT FOR RESEARCH CLARK, DAVID J Palo Alto, CA 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:

A major recent advancement for the field of pain research is the recognition of immune system dysregulation as a contributor to the most serious adverse consequences of pain from injury. Accumulating data from clinical and laboratory studies place the activation of B lymphocytes at the center of much of this work, particularly with respect to chronic pain and disability-related outcomes. Validation of this B cell hypothesis could lead directly to trials testing the efficacy of novel or existing immunomodulating agents on posttraumatic pain. To achieve these goals a well-validated core mouse model of limb fracture will be employed with additional studies to be conducted in incisional and nerve injury models to broaden the assessment of B cell mediated effects on pain. Age and sex will be included as variables to enhance rigor.
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.