Tissue Chips for Nociception, Opioid Addiction and Overdose

In 2019, NCATS — with support from the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative® — awarded five grants for research teams to create and test tissue chips to understand the mechanisms or effects of nociception (the sensory system’s response to harmful stimuli, including pain-relevant signaling), addiction and opioid use disorder. Tissue chips closely mimic human physiology, which makes them useful as models for studying biological processes and testing the toxicity, safety and efficacy of drugs.

The funded research, which totals approximately $158.2 million, is divided into two phases. In the first phase, researchers will develop and validate the nociception, addiction or overdose characteristics of their tissue chips. In the second phase, researchers will test the functionality of the tissue chips to understand pain or opioid pathway mechanisms, characterize tissue responses to pain or opioid therapeutics, identify new treatments for pain or addiction, or offer insights into improving current treatment efficacy.

These awards were made in response to RFA-TR-19-003.

View the project details below:

The University of Texas at Dallas

hiPSC-Based DRG Tissue Mimics on Multiwell Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception

Principal Investigator: Bryan James Black, Ph.D.

Grant Number: 1-UG3-TR-003149-01

Effective, nonaddictive alternatives to opioid-based pain management for chronic pain are needed urgently, but current models used to study nociception and test potential treatments are inadequate. This project seeks to develop a three-dimensional tissue-chip model of pain using a dorsal root ganglion (DRG) tissue mimic — comprising human-induced pluripotent stem cells (hiPSCs) and satellite glial cell surrogates — on a multiwell microelectrode array. The researchers aim to demonstrate the model’s capacity for testing hypotheses related to nonneuronal support cells and conduct moderate-throughput screening of potential alternative pain treatments.

Learn more about this project in NIH RePORTER.

Tulane University, University of Wisconsin and University of Central Florida

Human Microphysiological Model of Afferent Nociceptive Signaling

Principal Investigators: Michael J. Moore, Ph.D., Randolph S. Ashton, Ph.D., and Swaminathan Rajaraman, Ph.D.

Grant Number: 1-UG3-TR-003150-01

The management of acute and chronic pain can be challenging for both patients and clinicians. Next-generation neural microphysiological systems are needed to accelerate the development of pain treatments. This project will develop the first model of pain that uses living human cells on a chip to mimic the electrical transmission of pain signaling in the spinal cord, enabling evaluation of the cellular basis of tolerance to certain drugs. The resulting culture platform will be the only available human model of the spinal cord dorsal horn afferent circuit. The model eventually will enable experimental drugs to be screened more quickly, inexpensively and effectively.

Learn more about this project in NIH RePORTER.

University of Pittsburgh

Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets and an Empirical Strategy for Personalized Pain Management

Principal Investigators: Michael S. Gold, Ph.D., and Hang Lin, Ph.D.

Grant Number: 1-UG3-TR-003090-01

To help patients manage their osteoarthritis-associated joint pain, doctors often prescribe opioid drugs, which can be addictive; therefore, safe and effective methods are needed. This project aims to introduce sensory innervation into the microJoint, an in vitro multicomponent joint-on-a-chip system developed previously by the research team. The innervated microJoint — called the Neu-microJoint — will enable the study of the dynamic interplay between the peripheral nervous system and joint tissues. Ultimately, the Neu-microJoint will allow the identification of mechanisms responsible for pain associated with joint injury and thereby novel therapeutic targets, screening of therapeutic interventions, and implementation of personalized therapeutic strategies.

Learn more about this project on NIH RePORTER.

University of Central Florida and Cornell University

Multiorgan Human-on-a-Chip System to Address Overdose and Acute and Chronic Efficacy and Off-Target Toxicity

Principal Investigators: James J. Hickman, Ph.D., and Michael L. Shuler, Ph.D.

Grant Number: 1-UG3-TR-003081-01

Addiction to pain medications, especially opiates, has become a major public health crisis. To evaluate the effects of overdose treatments on recovery, efficacy and off-target toxicity, this project will build overdose models for fentanyl, methadone, codeine and morphine using human cells in a pumpless multiorgan system. The team will develop models for both male and female phenotypes, and models will be used to more accurately represent the effects of therapeutics on comorbidities related to opioid use. Once established, this system could be used to evaluate novel pain therapeutics and overdose treatments.

Learn more about this project on NIH RePORTER.

University of California, Los Angeles

Multiorgan-on-Chip Device for Modeling Opioid Reinforcement and Withdrawal and the Negative Affective Component of Pain: A Therapeutic Screening Tool

Principal Investigators: Nigel T. Maidment, Ph.D., Nureddin Ashammakhi, M.D., Ph.D., Stephanie Kristin Seidlits, Ph.D., and Clive Niels Svendsen, Ph.D.

Grant Number: 1-UG3-TR-003148-01

Opioid drugs are addictive because of changes in the activity of neurons in the brain that use dopamine as a neurotransmitter. Developing multiorgan-on-chip model systems that are based on human cells will help researchers search for drug treatments that can reverse such changes in activity and do not have addictive qualities. This project will develop multiorgan microphysiological systems on a three-dimensional platform. A major aim is to identify novel mechanisms contributing to chronic opioid-induced plasticity in dopamine responsiveness.

Learn more about this project on NIH RePORTER.