# hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception

> **NIH NIH UG3** · UNIVERSITY OF MASSACHUSETTS LOWELL · 2020 · $132,280

## Abstract

Project summary/abstract:
 Chronic pain afflicts up to one in five adults and is the most common cause of long-term disability in the
world. Opioids, which are commonly prescribed for non-cancer pain, are associated with a high incidence of
serious effects and abuse. Moreover, current in vivo and in vitro models used to study nociception and test
potential treatments are inadequate. Human-based, pathology-relevant models of nociception are urgently
needed to facilitate preclinical development of new non-opioid pain therapeutics. Therefore, we propose to
develop an innovative 3D model of acute and chronic nociception using hiPSC sensory neurons and satellite
glial cell surrogates (an hiPSC-based DRG tissue mimic) on multi-well MEAs.
 In the UG3 phase, we will develop a tissue chip for modeling acute and chronic nociception based on 3D
hiPSC-based dorsal root ganglion (DRG) tissue mimics and a high-content, moderate-throughput microelectrode
array (MEA) platform. DRG tissue mimics will be comprised of hiPSC counterparts to constituent intraganglionic
DRG cell types embedded in a collagen matrix. We will then demonstrate stable spontaneous and noxious
stimulus-evoked behavior in response to thermal, chemical, and electrical stimulation challenges. Furthermore,
we aim to demonstrate the clear functional and phenotypic advantages of utilizing a 3D mixed-cell DRG tissue
mimic versus purely neuronal 2D or 3D models. More specifically, we aim to demonstrate sensitivity to
translational control via ligand receptor interactions between neuronal and non-neuronal cell types, thereby
demonstrating pathological relevance to a the ‘holy trinity’ of pain (nociceptive, inflammatory and neuropathic)
and our model’s capacity for testing fundamental hypotheses related to contributions of non-neuronal support
cells in chronic pain development and maintenance.
 In the UH3 phase, we will demonstrate the powerful quantitative efficiency and preclinical efficacy of our
microphysiological system by detecting known ligand-based modulators of translational control and voltage-
gated ion channel antagonists in a sensitized model of chronic nociception. These two classes of drugs are
widely recognized as candidate compounds for reversing nociceptive plasticity and/or serving as peripheral
analgesics. Moreover, we will quantitatively define pharmacological hits based on widely accepted assay scoring
methodologies. Lastly, we will leverage the high-throughput nature or our tissue chip model to screen FDA-
approved, bioactive compounds, demonstrating the sensitivity and throughput of our high content assay, and
potentially identifying efficacy of candidate therapeutics obscured by less sophisticated methods of phenotypic
screening.

## Key facts

- **NIH application ID:** 10263436
- **Project number:** 3UG3TR003149-02S1
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS LOWELL
- **Principal Investigator:** Bryan James Black
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $132,280
- **Award type:** 3
- **Project period:** 2020-09-13 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263436

## Citation

> US National Institutes of Health, RePORTER application 10263436, hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception (3UG3TR003149-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10263436. Licensed CC0.

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