Translational Research to Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder

Overview 

The Research Need 

New interventions are needed to treat opioid misuse and addiction as well as to help people manage pain safely and effectively. Scientists need more accurate research models to understand how potential new drugs affect human biology.   

About the Program 

Through the National Center for Advancing Translational Sciences (NCATS), NIH provides translational science resources and technical expertise to researchers studying pain, addiction, and overdose. This program fosters collaboration between preclinical researchers at NIH-funded institutions and experts at the NCATS Intramural Division of Preclinical Innovation. NIH-funded scientists contribute background knowledge and a starting point for a particular project, and NCATS scientists bring an equivalent wealth of knowledge in translation – along with expertise to transform those starting points into useful tools and platforms for drug development. This research aims to advance knowledge about the underlying biology of pain, addiction, and overdose; develop novel platforms to facilitate therapeutic development; develop new treatments; and determine which ones are most effective.  

The program uses innovative artificial intelligence algorithms to predict and synthesize novel structures capable of interacting with specific targets; enables small-scale synthesis of predicted molecules; and incorporates in-line, rapid biological testing of those molecules. Through an iterative process, the resulting data are used to improve design, synthesis, and biological characteristics of molecules.  

The program also creates human tissue-based microphysiological systems, also known as tissue chips or “organs-on-chips.” These tools advance knowledge of how the nervous system responds to painful stimuli – as well as what mechanisms underlie acute and chronic pain, addiction, opioid use disorder, and overdose. 

Program Details

To date, through the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, NIH has provided support for ongoing collaborative research projects, prize awards, research grants, and supplements through the Translational Research To Advance Testing of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder Program.

Research Examples

Research examples supported by this program include:  

  • Performing preclinical testing of candidate therapeutics for treating pain and opioid use disorder 
  • Developing high-throughput screening methods to identify pharmacological probes 
  • Elucidating promising chemical structures for therapeutic candidates 
  • Developing an iterative learning and automated, modular platform to discover non-addictive pain medications 
  • Developing a closed-loop system integrating chemical, biological, and computational approaches for next-generation pain medications 
  • Developing and characterizing induced pluripotent stem cell-derived cell types relevant to nociception, addiction, and overdose 
  • Developing multicellular constructs that mimic the structure and function of tissues involved in pain, addiction, or overdose using relevant human primary or induced pluripotent stem cell-derived cells 
  • Determining cellular contributors to individual human susceptibility to different pain conditions  
  • Profiling epigenetic and cellular changes underlying human pain pathways

  • Tulane University – Louisiana
  • University of California, Los Angeles – California
  • University of Central Florida – Florida
  • University of Pittsburgh – Pennsylvania
  • University of Texas, Dallas – Texas

Funded Projects

2020
Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets, and an Empirical Strategy for Personalized Pain Management
Mar 19, 2020
2020
Human Microphysiological Model of Afferent Nociceptive Signaling
Mar 19, 2020
2020
Multi-organ human-on-a-chip system to address overdose and acute and chronic efficacy and off-target toxicity
Mar 19, 2020
2020
hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception
Mar 19, 2020
2020
Multi-organ-on-chip device for modeling opioid reinforcement and withdrawal, and the negative affective component of pain: a therapeutic screening tool.
Mar 19, 2020

Closed Funding Opportunities

2019
HEAL Initiative: Announcement of the NCATS ASPIRE Design Challenges to Develop Innovative and Catalytic Approaches Towards Solving the Opioid Crisis
Sep 25, 2019