Funded Projects

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Project # Project Title Research Focus Area Research Program Administering IC Institution(s) Investigator(s) Location(s) Year Awarded
1R61NS133217-01
A Novel Assay to Improve Translation in Analgesic Drug Development Preclinical and Translational Research in Pain Management Development and Optimization of Non-Addictive Therapies to Treat Pain NINDS VIRGINIA COMMONWEALTH UNIVERSITY NEGUS, SIDNEY S Richmond, VA 2023
NOFO Title: Development and Validation of Pain-Related Models and Endpoints to Facilitate Non-Addictive Analgesic Discovery
NOFO Number: NOT-NS-22-095
Summary:

Effective development of non-addictive therapies for pain requires animal models that reflect the human condition. Unfortunately, currently used models have limitations and have not always done a good job of predicting what will work in human patients. This project will refine a new way of measuring pain-related behaviors in mice that takes advantage of more natural mouse behavior and is less influenced by experimenter biases and artifacts. The research will verify that the promising results hold up in several different types of pain and that different classes of clinically used pain medications are effective. They will also make sure the data can be reproduced by an outside laboratory. If successful, this will support the use of this new read-out for future pain therapy development.
9R42NS120548-02A1
Development of KLS-13019 for Neuropathic Pain Cross-Cutting Research Small Business Programs NINDS KANNALIFE SCIENCES, INC. BRENNEMAN, DOUGLAS ERIC (contact); WARD, SARA J Lloyd Harbor, NY 2021
NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R41/R42 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-009
Summary:

Neuropathic pain adversely affects quality of life and remains challenging to treat, presenting high unmet medical need. One example of this type of pain, chemotherapy-induced peripheral neuropathy, is a chronic, severely debilitating consequence of cancer therapy for which there are no effective treatment strategies. This research is testing a new cannabidiol (CBD) analogue (KLS-13019) with neuroprotective properties and which has improved drug-like properties compared to CBD. This project will optimize the process to manufacture KLS-13019, develop analytical methods, optimize its formulation, evaluate its safety and toxicity, and test KLS-13019’s efficacy of in a rat model of chemotherapy-induced peripheral neuropathy.
5R01NS102432-02
AIBP and regulation of neuropathic pain Preclinical and Translational Research in Pain Management Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain NINDS Univ. of Calif., U.C. San Diego Miller, Yury La Jolla, CA 2018
NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

Persistent pain states arising from inflammatory conditions, such as in arthritis, diabetes, HIV, and chemotherapy, exhibit a common feature in the release of damage-associated molecular pattern molecules, which can activate toll-like receptor-4 (TLR4). Previous studies suggest that TLR4 is critical in mediating the transition from acute to persistent pain. TLR4 as well as other inflammatory receptors localize to lipid raft microdomains on the plasma membrane. We have found that the secreted apoA-I binding protein (AIBP) accelerates cholesterol removal, disrupts lipid rafts, prevents TLR4 dimerization, and inhibits microglia inflammatory responses. We propose that AIBP targets cholesterol removal to lipid rafts harboring activated TLR4. The aims of this proposal are to: 1) determine whether AIBP targets lipid rafts harboring activated TLR4; 2) test whether AIBP reduces glial activation and neuroinflammation in mouse models of neuropathic pain; and 3) identify the origin and function of endogenous AIBP in the spinal cord.
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.
1K99NS134965-01
Lymphocyte Antigen 6 (Ly6) Proteins: New Players in Chronic Pain Cross-Cutting Research Training the Next Generation of Researchers in HEAL NINDS NEW YORK UNIVERSITY GOMEZ, KIMBERLY New York, NY 2023
NOFO Title: HEAL Initiative Advanced Postdoctoral-to-Independent Career Transition Award in PAIN and SUD Research to Promote Diversity (K99/R00 Independent Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-025
Summary:

Neuropathic pain—a debilitating form of chronic pain affecting millions of people—responds poorly to current analgesic treatment approaches. By better understanding the cellular mechanisms and compounds involved in neuropathic pain, researchers will be able to develop more targeted therapeutic approaches. This project will investigate the role that two proteins—Ly6e and Lynx1—play in various processes involved in the development of neuropathic pain, such as the activity of pain-triggering sensory neurons, interactions between neurons and immune cells, and the activity of an ion channel that has been implicated in the generation of pain signals.