Screening of candidate analgesics using a patient‐derived human iPSC model of nociception identifies putative compounds for therapeutic treatment
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<sub>V</sub> 1.7 channel for targeted analgesia.
Authors
- Jack Thornton
- Thomas C. Henderson (ORCID: https://orcid.org/0000-0002-0792-3882)
- Majlinda Lako (ORCID: https://orcid.org/0000-0003-1327-8573)
- Sushma Nagaraja‐Grellscheid
- Evelyne Sernagor (ORCID: https://orcid.org/0000-0003-3803-257X)
- Lyle Armstrong (ORCID: https://orcid.org/0000-0002-7234-9362)
- Franziska Görtler (ORCID: https://orcid.org/0000-0003-2015-5766)
- Vsevolod Telezhkin (ORCID: https://orcid.org/0000-0002-5054-8774)
- Alberto Capurro (ORCID: https://orcid.org/0000-0001-6773-6512)
- sally harwood
- Adrienne Unsworth
Institutions
- University of Bergen (NO)
- Newcastle University (GB)
Publication Details
- Journal
- Clinical and Translational Medicine
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1002/ctm2.70339
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Medical Research Council