Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
3U44NS115692-01S1
Development and Optimization of MNK Inhibitors for the Treatment of Neuropathic Pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS 4E THERAPEUTICS INC. SAHN, JAMES JEFFREY Austin, TX 2020
NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

There is an urgent unmet need for more efficacious analgesics that act via a non-opioid pathway. Mitogen Activated Protein Kinase-interacting kinase 2 (MNK2) is an enzyme that has been implicated in pain signaling, and there is compelling evidence that inhibiting MNK2 has significant pain-reducing effects with few side-effects. Since MNK2 selective inhibitors have not yet been identified, selective inhibition of MNK2 with a small molecule has not been possible. The development of such compounds will enable studies that will illuminate key differences between MNK2 and MNK1. More importantly, from a therapeutic standpoint, highly selective MNK2 inhibitors may prove to have enhanced efficacy and a more favorable side-effect profile than molecules that inhibit both MNK2 and MNK1. This project will support the design and synthesis of at least one MNK2 inhibitor, with >100-fold selectivity over MNK1, that may be developed into a lead compound for treating neuropathic pain.
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.
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.
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.
1R01DE029951-01
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 NINDS COLUMBIA UNIVERSITY HEALTH SCIENCES BUNNETT, NIGEL W; SCHMIDT, BRIAN L New York, NY 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:

Many non-opioid drugs target G Protein-Coupled Receptors (GPCRs), a family of proteins involved in many pathophysiological processes including pain, fail during clinical trials for unknown reasons. A recent study found GPCRs not only function at the surface of nerve cells but also within a cell compartment called the endosome, where their sustained activity drives pain. This study will build upon this finding and test whether the clinical failure of drugs targeting plasma membrane GPCRs is related to their inability to target and engage endomsomal GPCRs (eGPCRs). This study will use stimulus-responsive nanoparticles (NP) to encapsulate non-opioid drugs and selectively target eGPCR dyads to investigate how eGCPRs generate and regulate sustained pain signals in neuronal subcellular compartments. This study will also validate eGCPRs as therapeutic targets for treatment of chronic inflammatory, neuropathic and cancer pain. Using NPs to deliver non-opioid drugs, individually or in combinations, directly into specific compartments in nerve cells could be a potential strategy for new pain therapies.
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. 
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.
5R01NS097880-02
Regulation of neuropathic pain by exercise: effects on nociceptor plasticity and inflammation Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS DREXEL UNIVERSITY DETLOFF, MEGAN R Philadelphia, PA 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Spinal cord injury (SCI) impairs sensory transmission leading to chronic, debilitating neuropathic pain. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. In the lab, we have shown the timing of exercise is critical to meaningful sensory recovery. Early administration of a sustained locomotor exercise program in spinal cord–injured rats prevents the development of neuropathic pain, while delaying similar locomotor training until pain was established was ineffective at ameliorating it. The time elapsed since the injury occurred also indicates the degree of inflammation in the dorsal horn. We have previously shown that chronic SCI and the development of neuropathic pain correspond with robust increases in microglial activation and the levels of pro-inflammatory cytokines. This proposal seeks to lengthen the therapeutic window where rehabilitative exercise can successfully suppress neuropathic pain by pharmacologically reducing inflammation in dorsal root ganglia.
3R01NS097880-02S1
VALIDATION OF TARGETING MACROPHAGE-MEDIATED EVENTS IN THE DRG TO ALLEVIATE CHRONIC SPINAL CORD INJURY PAIN Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS DREXEL UNIVERSITY DETLOFF, MEGAN R PHILADELPHIA, PA 2019
NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Spinal cord injury (SCI) impairs sensory transmission and leads to chronic, debilitating neuropathic pain. While our understanding of the development of chronic pain has improved, the available therapeutics provide limited relief. We will examine the peripheral immune and inflammatory response. Secondary inflammation in response to SCI is a series of temporally ordered events: an acute, transient upregulation of chemokines, followed by the recruitment of monocytes/macrophages and generation of an inflammatory environment at the lesion site in the spinal cord, but also surrounding primary nociceptors in the dorsal root ganglia (DRG). These events precede neuropathic pain development. Previous work indicates that after SCI, macrophage presence in the DRG correlates with neuropathic pain. We propose to study: 1) whether the phenotype of macrophages that infiltrate the DRG is different than those that persist chronically after SCI and 2) how manipulation of macrophage phenotype affects nociceptor activity and pain development.
5R01DE027454-02
Modeling temporomandibular joint disorders pain: role of transient receptor potential ion channels Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDCR Duke University Chen, Yong Durham, NC 2019
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Masticatory and spontaneous pain associated with temporomandibular joint disorders (TMJD) is a significant contributor to orofacial pain, and current treatments for TMJD pain are unsatisfactory. Pain-related transient receptor potential (TRP) channels, expressed by trigeminal ganglion (TG) sensory neurons, have been implicated in both acute and chronic pain and represent possible targets for anti-pain strategies. Using bite force metrics, we found TMJ inflammation-induced masticatory pain to be significantly, but not fully, reversed in Trpv4 knockout mice, suggesting the residual pain might be mediated by other pain-TRPs. Our gene expression studies demonstrated that TRPV1 and TRPA1 were up-regulated in the TG in response to TMJ inflammation in a Trpv4-dependent manner. We hypothesize that TRPV1 and TRPA1, like TRPV4, contribute to TMJ pain. Our specific aims will examine the contribution of TRPV1, TRPV4, and TRPA1 to pathogenesis of TMJD pathologic pain including assessment of the role of neurogenic inflammation.
1RF1NS131812-01A1
Targeting Checkpoint Inhibitors for Pain Control Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS DUKE UNIVERSITY JI, RU-RONG Durham, NC 2023
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-034
Summary:

Immune checkpoint proteins regulate the immune system to prevent it from indiscriminately attacking cells. Some cancers activate these immune checkpoints to avoid attack, and drugs that target certain immune checkpoints are approved for cancer treatment. The same pathway may also be involved in pain because immune checkpoint proteins, such as programmed death 1 (PD-1) and the molecule that binds to it (programmed death ligand 1 [PD-L1]), also are found in sensory neurons, microglia, and macrophages. This project will investigate PD-1/PD-L1 in different cell populations to determine their contribution to pain and to the effects of opioids such as morphine. This knowledge may help identify new drugs for pain management that modify immune checkpoint activity.
1R01DE029342-01
Identification and Validation of a Novel Central Analgesia Circuit Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDCR DUKE UNIVERSITY WANG, FAN Durham, NC 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

This project focuses on identifying and validating a new central analgesic circuit in the brain, based on a highly innovative hypothesis that the strong analgesic effects of general anesthesia (GA) are in part carried out by GA-mediated activation of the endogenous analgesic circuits. Preliminary discovery studies found that a subset of GABAergic neurons located in the central amygdala (CeA) become strongly activated and express high levels of the immediate early gene Fos under GA (hereafter referred to as CeAGA neurons). Furthermore, activation of these neurons exert profound pain-suppressing effects in an acute pain model and a chronic orofacial neuropathic pain model in mice. Based on these exciting preliminary findings, this project will identify and validate CeAGA neurons’ analgesic functions utilizing multiple mouse pain models. Identification of these shared common pathways that need to be suppressed by specific subtypes of CeAGA analgesic neurons will be highly critical for developing precise CeAGA-targeted therapies to treat chronic pain.
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.
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.
1R01DK123138-01
Validation of peripheral CGRP signaling as a target for the treatment of pain in chronic pancreatitis Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NIDDK JOHNS HOPKINS UNIVERSITY PASRICHA, PANKAJ J Baltimore, MD 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Chronic pancreatitis (CP) and the debilitating pain associated with it remains a common and challenging clinical syndrome that is difficult to treat effectively. Using rodent models of CP, preliminary studies have found that nerve growth factor (NGF) and transforming growth factor beta (TGFb) appear to be acting by the common effector, calcitonin-gene related peptide (CGRP), to induce pain in CP. CGRP is known to mediate pain as a neurotransmitter in the central nervous system, specifically as a potent vasodilator involved in migraine. This project will test the hypothesis that peripheral CGRP is a major mediator of peripheral nociceptive sensitization in CP, and that peripherally restricted anti-CGRP treatment could provide an efficient and sufficient approach for the treatment of pain in pancreatitis
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.
1RF1NS134549-01
Validation of a New Large-Pore Channel as a Novel 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 JOHNS HOPKINS UNIVERSITY QIU, ZHAOZHU (contact); GUAN, YUN Baltimore, MD 2023
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-034
Summary:

Activation of immune cells (microglia) in the central nervous system and neuroinflammation have emerged as key drivers of neuropathic pain. These processes can be triggered by release of ATP, the compound that provides energy to many biochemical reactions. The source and mechanism of ATP release are poorly understood but could be targets of novel treatment approaches for neuropathic pain. This project will use genetic, pharmacological, and electrophysiological approaches to determine whether a large pore channel called Swell 1 that spans the cell membrane is the source of ATP release and resulting neuropathic pain and thus could be a treatment target.
1RF1NS113883-01
Sympathetic-mediated sensory neuron cluster firing 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 JOHNS HOPKINS UNIVERSITY DONG, XINZHONG Baltimore, MD 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

An important component of neuropathic pain is spontaneous or ongoing pain, such as burning pain or intermittent paroxysms of sharp and shooting pain, which may result from abnormal spontaneous activity in sensory nerves. However, due to technical limitations, spontaneous activity in sensory neurons in vivo has not been well studied. Using in vivo imaging in genetically-modified mice, preliminary findings identified spontaneously-firing clusters of neurons formed within the dorsal root ganglia (DRG) after traumatic nerve injury that exhibits increased spontaneous pain behaviors. Furthermore, preliminary evidence has been collected that cluster firing may be related to abnormal sympathetic sprouting in the sensory ganglia. This project will test the hypothesis that cluster firing is triggered by abnormal sympathetic inputs to sensory neurons, and that it underpins spontaneous paroxysmal pain in neuropathic pain models. Findings from this project will identify potential novel therapeutic targets for the treatment of neuropathic pain.
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.
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.
1R01NS131165-01A1
Validation of Neuropilin-1 Receptor Signaling in Nociceptive Processing Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS NEW YORK UNIVERSITY KHANNA, RAJESH New York, NY 2023
NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-034
Summary:

Neuropilin 1 receptor (NRP1) is a protein receptor that is active in neurons and is hypothesized to be a key mediator of sensory neuron sensitization that can lead to pain. This project will study the cellular mechanisms by which NRP1 leads to sensitization and which cell types—sensory neurons, microglia, or both—are responsible for NRP1’s role in pain. The findings can help validate NRP1 in sensory neurons and the spinal cord as a target to treat pain following nerve injury.
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.
5R01NS104295-03
Cellular and Molecular Role of CXCR4 signaling in Painful Diabetic Neuropathy Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS Northwestern University MENICHELLA, DANIELA M Evanston, IL 2019
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Neuropathic pain is a debilitating affliction present in 26% of diabetic patients, with substantial impact on the quality of life. Despite this significant impact and prevalence, current therapies for painful diabetic neuropathy (PDN) are only partially effective, and the molecular mechanisms underlying neuropathic pain in diabetes are not well understood. Our long-term goal is to elucidate the molecular mechanisms responsible for PDN in order to provide targets for the development of therapeutic agents. Our objective is to identify the molecular cascade linking CXCR4/SDF-1 chemokine signaling to DRG nociceptor hyper-excitability, neuropathic pain, and small fiber degeneration. Our aims will determine: 1) the ion-channel current profile of the nociceptor hyper-excitable state produced by CXCR4/SDF-1 signaling in PDN; 2) the gene expression profile of the nociceptor hyper-excitable state produced by CXCR4/SDF-1 signaling in PDN; and 3) the specific features of nociceptor mitochondrial dysfunction produced by CXCR4/SDF-1 signaling in PDN.
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.
1RF1NS113881-01
Discovery and validation of a new long noncoding RNA as a novel 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 RBHS-NEW JERSEY MEDICAL SCHOOL TAO, YUAN-XIANG Newark, NJ 2019
NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Identification of new targets and mechanisms underlying chronic neuropathic pain is essential for the discovery of novel treatments and preventative tactics for better neuropathic pain management. A recent exploration of next-generation RNA sequencing identified a large, native, full-length long noncoding RNA (lncRNA) in mouse and human dorsal root ganglion (DRG). It was named as nerve injury-specific lncRNA (NIS-lncRNA), since its expression was found increased in injured DRGs, in response to peripheral nerve injury, but not in response to inflammation. Preliminary findings revealed that blocking the nerve injury-induced increases in DRG NIS-lncRNA levels ameliorated neuropathic pain. This project will validate NIS-lncRNA as a therapeutic target in animal models of neuropathic pain and in cell-based functional assays utilizing human DRG neurons. Completion of this proposal will advance neuropathic pain management and might provide a novel, non-opioid pain therapeutic target.