Discovery and Validation of Novel Targets for Safe and Effective Treatment of Pain

Research Spotlights

Dr. William Renthal talks about studying nerve cell molecules to find new pain treatments.

Video: What Makes Pain-Sensing Nerve Cells Unique?

Image of hip sciatica pain for the orphan GPCR spotlight

Unlocking the Secrets of Nerve Pain

A New Pain-Suppression Center in the Brain

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 early stage (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, as well as for new animal models to test the effectiveness of new medications on these targets.

About the Program

This program aims to identify new, non-addictive biological targets in the peripheral and central nervous systems, as well as in the immune system and other body organs and tissues involved in detecting and transmitting pain signals. The 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.

To validate targets, this research employs knockout animals or human tissue and supports independent replication of results. The program identifies and validates small molecules and biologics (such as antibodies and cell-based therapies) that could lead to translational research to develop pain therapeutics. The program also develops, characterizes, and validates animal models of pain and develops reliable pain outcome measures. That includes both rodents and animals that are more similar to humans in size, anatomy, and physiology.

PRECISION Human Pain Network

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 focuses on research efforts to identify and describe mechanisms underlying pain experiences in humans rather than animal models. The PRECISION network coordinates, curates, harmonizes, and integrates comprehensive datasets generated from this research. The network’s human-focused research capitalizes on recent technological advances to study human tissues and cells involved in pain processing. A key goal is to identify molecular signatures, cell types, and cellular function signatures that underlie human pain pathways. These activities will enable future translational research and the development of non-addictive pain therapies for human pain conditions.

Open Funding Opportunities

2022

HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)

NOFO Link

Jan 07, 2022

NOFO Link

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Upcoming Events

HEAL Pain Partnering Meeting - October 4 – 5, 2023

Program Details

To date, through the Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®, NIH has funded 47 awards for this program, totaling $90.3 million.

Research Examples

Research examples supported by this program include:

Determining the contribution of peptidase inhibitor 16 to chronic pain using mouse models and human tissues 
Evaluating the role of molecular interactions on spinal cord sensitization, excitatory synapse formation, and pain state development in models of neuropathic pain
Validating vascular endothelial growth factor receptors 1 and 2 as novel therapeutic targets for osteoarthritis pain 
Determining mechanisms of activation of sympathetically mediated sensory neurons thought to be involved in spontaneous pain
Developing a range of non-rodent animal models of pain
Identifying animal behaviors and other outcomes that can be used to measure pain
Analyzing individual human cells to determine how human pain receptors communicate pain signals throughout the nervous system
Analyzing gene expression of individual cells in pain nerve cell clusters in individuals with and without pain

4E Therapeutics Inc. – Texas
Brigham and Women's Hospital – Massachusetts
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