A highly efficient method to differentiate CGRP-expressing peptidergic nociceptors from human induced pluripotent stem cells

Duggal, Galbha, Li, Xinyu, Pettingill, Philippa, Lalic, Tatjana, Gupta, Shailesh Kumar, Høgsbro, Christine Flodgaard, Volpato, Viola, Webber, Caleb ORCID: https://orcid.org/0000-0001-8063-7674, Bowden, Rory, Charou, Despoina, Arunasalam, Kanisa, Maresca, Marcello, Hicks, Ryan, Chintawar, Satyan and Cader, M. Zameel 2026. A highly efficient method to differentiate CGRP-expressing peptidergic nociceptors from human induced pluripotent stem cells. Stem Cell Reports 21 (7) , 102971. 10.1016/j.stemcr.2026.102971

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Abstract

Pain disorders such as neuropathic pain and headache remain areas of considerable unmet need and considered high risk by pharma. Human-induced pluripotent stem cells (iPSC)-derived sensory neurons have already been used to accelerate translational research but the current differentiation protocols produce non-peptidergic nociceptors. We demonstrate for the first time the robust differentiation of hiPSC into peptidergic nociceptor lineage with high yield. These nociceptors express CGRP and TRPV1 and show functional maturity including the expression of TTX-resistant currents and responding to TRPV1 and TRPA1 agonists. Importantly, they were able to release CGRP basally and upon stimulation by inflammatory soup, which was inhibited upon the application of the 5-HT1B/1D/1F agonist, sumatriptan, a migraine prophylactic drug. We report the successful generation of a novel in vitro functional peptidergic nociceptor model which will allow investigation of disease mechanisms in pain and translational phenotypic drug screening for new effective pain therapies.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Elsevier BV
ISSN:	2213-6711
Date of First Compliant Deposit:	7 July 2026
Date of Acceptance:	21 May 2026
Last Modified:	05 Aug 2026 15:24
URI:	https://orca.cardiff.ac.uk/id/eprint/188000

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