Evidence map›Paper›PMID 40415465›Full record

ArticleClinical and translational medicine2025

Screening of candidate analgesics using a patient-derived human iPSC model of nociception identifies putative compounds for therapeutic treatment.

Jack R Thornton, Alberto Capurro, Sally Harwood, Thomas C Henderson, Adrienne Unsworth, Franziska Görtler, Sushma Nagaraja-Grellscheid, Vsevolod Telezhkin, Majlinda Lako, Evelyne Sernagor and 1 more

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jack R ThorntonBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Alberto CapurroBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Sally HarwoodBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Thomas C HendersonBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Adrienne UnsworthBioinformatics Support Unit, Newcastle University, Newcastle-upon-Tyne, UK.
Franziska GörtlerDepartment of Biological Sciences, University of Bergen, Bergen, Norway.
Sushma Nagaraja-GrellscheidDepartment of Biological Sciences, University of Bergen, Bergen, Norway.
Vsevolod TelezhkinSchool of Dental Sciences, Newcastle University, Newcastle-upon-Tyne, UK.
Majlinda LakoBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Evelyne Sernagor *Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Lyle ArmstrongBiosciences Institute, Newcastle University, Newcastle-upon-Tyne, UK.ORCID 0000-0002-7234-9362

Funding

Medical Research Council MC_PC_19047Medical Research Council MR/R011338/1
6 · The paper itself

Abstract

background and purposeIn this study, we applied an induced pluripotent stem cell (iPSC)-based model of inherited erythromelalgia (IEM) to screen a library of 281 small molecules, aiming to identify candidate pain-modulating compounds. EXPERIMENTAL APPROACH: Human iPSC-derived sensory neuron-like cells, which exhibit action potentials in response to noxious stimulation, were evaluated using whole-cell patch-clamp and microelectrode array (MEA) techniques. KEY

resultsSensory neuron-like cells derived from individuals with IEM showed spontaneous electrical activity characteristic of genetic pain disorders. The drug screen identified four compounds (AZ106, AZ129, AZ037 and AZ237) that significantly decreased spontaneous firing with minimal toxicity. The calculated IC CONCLUSIONS AND IMPLICATIONS: Our screening approach demonstrates the reproducibility and effectiveness of human neuronal disease modelling offering a promising avenue for discovering new analgesics. These findings address a critical gap in current therapeutic strategies for both general and neuropathic pain, warranting further investigation. This study highlights the innovative use of patient-derived iPSC sensory neuronal models in pain research and emphasises the potential for personalised medicine in developing targeted analgesics. KEY POINTS: Utilisation of human iPSCs for efficient differentiation into sensory neuron-like cells offers a novel strategy for studying pain mechanisms. IEM sensory neuron-like cells exhibit key biomarkers and generate action potentials in response to noxious stimulation. IEM sensory neuron-like cells display spontaneous electrical activity, providing a relevant nociceptive model. Screening of 281 compounds identified four candidates that significantly reduced spontaneous firing with low cytotoxicity. Electrophysiological profiling of selected compounds revealed promising insights into their mechanisms of action, specifically modulating the Na

Indexed as

AnalgesicsErythromelalgiaInduced Pluripotent Stem CellsNociceptionAction PotentialsDrug Evaluation, PreclinicalHumansSensory Receptor CellsAnalgesicsanalgesic candidatesdrug screeningelectrophysiologyinduced pluripotent stem cells (iPSCs)inherited erythromelalgia (IEM)sensory neuron

Identifiers

PMID40415465
PMCPMC12104564

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.