# Human Microphysiological Model of Afferent Nociceptive Signaling

> **NIH NIH UH3** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $1,978,863

## Abstract

PROJECT SUMMARY
 The management of pain—both acute and chronic—can be a frustratingly futile endeavor for both patients
and clinicians. Desperate attempts at treatment with opioids and other narcotics has led to a heartbreaking and
calamitous epidemic of addiction to prescription painkillers. This epidemic has prompted federal agencies and
the pharmaceutical industry to work toward the identification of the next generation of analgesics. Unfortunately,
there are few adequate model systems currently in use to enable rapid screening of the analgesic properties of
drug candidates. There is an acute need for next-generation neural microphysiological systems that are useful
for identifying drug candidates for problems such as pain. Most current microphysiogical models of the nervous
system tend toward two categories: organoids and microfluidic/ microelectrode chips. We postulate that the
unique complexity and structure of the nervous system demand an integrated approach in order to realize
designs of neural microphysiological systems that can begin to account for the basic physiological units that
assemble to produce emergent behaviors of the nervous system.
 We propose to develop a human cell-based model of the afferent pain pathway in the dorsal horn of the
spinal cord. Our approach is innovative because it utilizes novel human pluripotent stem cell (hPSC)-derived
phenotypes in a model that combines the 3D nature of organoid culture with the structural and organizational
specificity of microfabricated systems, all on an integrated, custom 3D microelectrode array. The resulting culture
platform will be the only available human model of the dorsal horn afferent circuit. The objectives of the proposal
will be met in two phases. In the first, we will establish the feasibility of a physiologically relevant, human, 3D
model of the afferent pain pathway that will be useful for evaluation of candidate analgesic drugs. In the second
phase, we will then improve the physiological relevance of the system by promoting neural network maturation
before then demonstrating the system’ utility in modeling adverse effects of opioids and screening a library of
compounds to validate the model. Completion of the objective will establish novel protocols for deriving dorsal
horn neurons from hPSCs and create the first human microphysiological model of the spinal cord dorsal horn
afferent sensory pathway.

## Key facts

- **NIH application ID:** 10348860
- **Project number:** 4UH3TR003150-02
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Randolph S Ashton
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,978,863
- **Award type:** 4N
- **Project period:** 2019-09-26 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348860

## Citation

> US National Institutes of Health, RePORTER application 10348860, Human Microphysiological Model of Afferent Nociceptive Signaling (4UH3TR003150-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10348860. Licensed CC0.

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