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

Overview

The Research Need

The overreliance on prescription opioids for the management of chronic pain conditions, despite limited effectiveness among some patients, has contributed to the recent epidemic of deaths due to opioid overdose. There is an urgent need to develop effective and non-addictive therapeutics for acute and chronic pain conditions that requires the scientific discovery of biological targets.

About the Program

This program seeks to accelerate the scientific discovery and validation of novel treatment targets for acute and chronic pain conditions, to speed the development of effective non-addictive medications for pain and reduce the reliance on opioid medications.

Identifying new targets for the treatment of pain will involve rigorous validation studies, with multiple approaches and reproducibility testing in multiple laboratories.

This program will:

  • Enable the basic research discovery of biological targets in the peripheral and central nervous system, as well as in the immune and other tissue systems in the body that are critically involved in detecting and transmitting painful signals under pathological and disease conditions.
  • Accelerate rigorous validation of targets for the development of effective treatments for pain, with minimal side effects and little to no abuse or addiction liability.
  • Establish multiple pain therapeutic targets for small molecules and biologics such as antibodies and cell-based therapies that could lead to translational and clinical studies and testing in humans.

The funded projects will thoroughly validate these therapeutic targets using a variety of methods and model systems. This in-depth basic research approach will enable future researchers to apply these targets to translational research and the development of non-addictive pain therapies.

Program Details

Through the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, NIH awarded 25 research grants and 18 administrative supplement awards, which total approximately $69 million. These awards are funded by multiple NIH Institutes and Centers. The goal of this research is to identify and validate novel targets for pain treatment.

Research Examples

The funded research for this program will analyze potential therapeutic targets for pain management.

Examples of research to be undertaken include:

  • Using a variety of models for pain, including orofacial chronic pain, traumatic nerve injury, chemotherapy-induced neuropathic pain, chronic pancreatitis, and other conditions
  • Analyzing a diverse range of therapeutic targets, including receptors on neurons and immune cells; gene expression regulators; long noncoding RNAs; and proteins involved in synapse formation, immune response, and nociception
  • Understanding physiological events that can be altered to reduce pain, such as turning on the central neuronal circuit that is activated under general anesthesia and reducing the spontaneous activity of sensory neurons that causes chronic pain
  • Using multiple cell-based and animal models and targeting validation studies to understand the differences and transition between acute and chronic pain
  • Using a variety of innovative techniques and testing potential drugs, biologicals, and genetic ways to validate targets and find non-addictive therapies for pain
  • Identify and validate new pain and opioid use disorder targets from within the understudied Druggable Genome

  • 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
  • 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

2020
Anatomic, Physiologic and Transcriptomic Mechanisms of Neuropathic Pain in Human DRG
Sep 29, 2020
2020
B Lymphocyte-Mediated Autoimmunity in Pain After Trauma
Sep 29, 2020
2020
Development and Optimization of MNK Inhibitors for the Treatment of Neuropathic Pain
Sep 29, 2020
2020
FKBP51 Antagonism to Prevent Chronic Pain: Optimizing Efficacy & Evaluating Safety and Mechanisms
Sep 29, 2020
2020
VALIDATION OF TARGETING MACROPHAGE-MEDIATED EVENTS IN THE DRG TO ALLEVIATE CHRONIC SPINAL CORD INJURY PAIN
Mar 19, 2020