# The Pain in a Dish Assay (PIDA): a high throughput system featuring human stem cell-derived nociceptors and dorsal horn neurons to test compounds for analgesic activity

> **NIH NIH R43** · VALA SCIENCES, INC. · 2023 · $350,064

## Abstract

Pain causes widespread human suffering and loss of productivity across society. Opioids, widely prescribed to
treat pain, are addictive, leading to a national surge in drug abuse and deaths resulting from opioid overdose.
This Phase I SBIR proposal, submitted in response to solicitation RFA-NS-23-006 (HEAL INITIATIVE:
Development of Therapies and Technologies Directed at Enhanced Pain Management), will initiate development
of the “Pain in a Dish Assay” (PIDA) to enable screening of compounds to identify potential analgesics to serve
as alternatives to opioids. The project will be a collaboration between Vala Sciences Inc., which specializes in
automated digital microscopes and cell-based assays for drug discovery, and Anatomic Incorporated, which
manufactures neurons derived from human induced pluripotent stem cell (hiPSCs). Dr. Tony Yaksh, an expert
on preclinical pain research, will be a consultant. Anatomic has developed functional hiPSC-nociceptors (dubbed
RealDRGs), which represent peripheral neurons specialized to respond to noxious stimuli, whose cell bodies
reside in the dorsal root ganglia. Similar to primary DRGs, RealDRGs respond to noxious stimuli (e.g., capsaicin,
the active ingredient in chili peppers) with large increases in intracellular calcium. Anatomic has also initiated
development of neurons that represent dorsal horn neurons of lamina I and II (dubbed hiPSC-DLNs), which are
the next step in neuronal pain transmission (nociceptors connect to DLNs). Vala’s Kinetic Image Cytometer (KIC)
is an automated microscope designed to quantify effects of compounds on calcium and voltage transients for
neurons cultured in 96- or 384-well dishes. For the PIDA, RealDRGs will be loaded with a calcium indicator, and
effects of potential pain modulators on responses to noxious stimuli will be quantified with the KIC. Furthermore,
an advanced version of the PIDA will be developed in which RealDRGs and hiPSC-DLNs are cocultured in a
device that features two wells connected via micro tunnels which will enable the RealDRGs to establish synaptic
connections with the hiPSC-DLNs. This will enable visualization of neuronal transmission between these cell
types initiated in response to noxious stimuli applied to the RealDRGs. The PIDA will enable discovery of pain
modulators that reduce responses of nociceptors to noxious stimuli, or reduce transmission of signals between
nociceptors and DLNs, a mechanism that has been relatively unexplored for pain management and for which
there are no in vitro models. The PIDA will feature human neurons, which will likely be more predictive of clinical
effects vs. animal models, leading to more efficient preclinical drug discovery, and reduced use of animals. The
PIDA, RealDRGs, hiPSC-DLNs, and KIC will be marketed to pharmaceutical companies and used for contract
research to develop novel, non-opioid, analgesics.

## Key facts

- **NIH application ID:** 10759735
- **Project number:** 1R43TR004743-01
- **Recipient organization:** VALA SCIENCES, INC.
- **Principal Investigator:** PATRICK M MCDONOUGH
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $350,064
- **Award type:** 1
- **Project period:** 2023-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10759735

## Citation

> US National Institutes of Health, RePORTER application 10759735, The Pain in a Dish Assay (PIDA): a high throughput system featuring human stem cell-derived nociceptors and dorsal horn neurons to test compounds for analgesic activity (1R43TR004743-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10759735. Licensed CC0.

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