Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain
Overview
The Research Need
Pain is a major factor in many acute and chronic conditions, but only a small number of new therapeutics for pain advance from Phase 1 clinical trials to approval by the U.S. Food and Drug Administration. There is an urgent need for innovative approaches to find and validate new biological targets for treating pain.
About the Program
This program seeks to accelerate the scientific discovery and validation of treatment targets for acute and chronic pain conditions in order to reduce reliance on opioid medications and speed the development of effective pain medications that have little or no abuse liability. This research enables basic discovery of biological targets in the peripheral and central nervous systems, as well as in the immune and other body systems involved in detecting and transmitting painful signals across diseases. This research also explores understudied genes and proteins (the druggable genome and proteome) associated with pain, pain perception, and opioid use disorder that might serve as markers or targets for treatment.
The program conducts rigorous validation of identified pain targets to ensure they have minimal side effects and little to no abuse or addiction liability. Validation approaches include use of knockout animals or human tissue, as well as reproduction of experiments by an independent laboratory. Research in the program also identifies and validates small molecules and biologics such as antibodies and cell-based therapies that could lead to translational research to develop pain therapeutics.
Within this program, the Program to Reveal and Evaluate Cells-to-Gene Information that Specify Intricacies, Origins, and the Nature of Human Pain (PRECISION Human Pain) network will capitalize on recent technological advances to understand the cellular and molecular characteristics of human tissues involved in pain processing. This information will be used to validate human therapeutic targets using a variety of cellular assay systems and reproducibility testing in multiple laboratories. This cutting-edge research approach will enable future translational research and the development of non-addictive pain therapies for human pain conditions.
Program Details
Through the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, NIH has awarded research grants and administrative supplements to identify and validate novel targets for pain treatment.
Research Examples
Research examples supported by this program include:
- Validating nuclear factor erythroid-2-related factor 2 as a non-addictive target for neuropathic pain
- Determining the contribution of peptidase inhibitor 16 to chronic pain using mouse models and human tissues
- Evaluating the role of calcium channel and thrombospondin-4 interactions on spinal cord sensitization, excitatory synapse formation, and pain state development in neuropathic pain models
- Validating vascular endothelial growth factor receptors 1 and 2 as novel therapeutic targets for osteoarthritis pain
- Assessing the role of FK506-binding protein 51 in post-traumatic stress exposure-induced pain
- Determining mechanisms of sympathetically mediated sensory neuron activation thought to be involved in spontaneous pain
- Defining the contribution of amylin 1 receptors to migraine pain
- Genetically and pharmacologically validating collapsin response mediator protein 2 phosphorylation as a novel target for neuropathic pain
- 4E Therapeutics Inc. – Texas
- Columbia University Health Sciences – New York
- Drexel University – Pennsylvania
- Duke University – North Carolina
- Ichan School of Medicine at Mount Sinai – New York
- Johns Hopkins University – Maryland
- New York University – New York
- Northwestern University – Illinois
- Palo Alto Veterans Institute for Research – California
- Research Triangle Institute - North Carolina
- Rutgers Biomedical and Health Sciences-New Jersey Medical School – New Jersey
- Rush University Medical Center – Illinois
- Stanford University – California
- State University of New York at Buffalo – New York
- St. Louis University – Missouri
- The University of Texas, Dallas – Texas
- The University of Texas MD Anderson Cancer Center, Houston – Texas
- University of Arizona – Arizona
- University of California, Irvine – California
- University of California, San Diego – California
- University of California, San Francisco – California
- University of Cincinnati – Ohio
- University of Illinois, Chicago – Illinois
- University of Iowa – Iowa
- University of Maryland, Baltimore – Maryland
- University of Minnesota – Minnesota
- University of North Carolina, Chapel Hill – North Carolina
- University of Pittsburgh – Pennsylvania
- University of Texas Health Science Center at San Antonio – Texas
- Washington University – Missouri
Funded Projects
Open Funding Opportunities
Closed Funding Opportunities
Contact
Michael L. Oshinsky, Ph.D.
NINDS
D.P. Mohapatra, Ph.D.
NINDS
Participating NIH Institutes, Centers, and Offices
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Cancer Institute (NCI)
- National Eye Institute (NEI)
- National Institute on Aging (NIA)
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- National Institute of Dental and Craniofacial Research (NIDCR)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute on Drug Abuse (NIDA)
- National Institute of Nursing Research (NINR)
- National Library of Medicine (NLM)
- National Center for Complementary and Integrative Health (NCCIH)
- National Center for Advancing Translational Sciences (NCATS)
View Other Research Programs in This Focus Area
- Development and Optimization of Non-Addictive Therapies to Treat Pain
- Preclinical Screening Platform for Pain (PSPP)
- Restoring Joint Health and Function to Reduce Pain Consortium (Re-JOIN)
- Translating Discoveries into Effective Devices to Treat Pain
- Translational Research to Advance Testing of Novel Drugs and Human Cell-based Screening Platforms to Treat Pain and Opioid Use Disorder