An in vitro platform for characterizing axonal electrophysiology of individual human iPSC-derived nociceptors

Neuropathic pain is characterized by aberrant activity of specific nociceptor populations, as demonstrated through functional assessments such as microneurography. Current treatments against severe forms of neuropathic pain demonstrate insufficient efficacy or lead to unwanted side effects as they f...

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Bibliographic Details
Published in:Biosensors & bioelectronics Vol. 281; p. 117418
Main Authors: Clément, Blandine F., Petrella, Lorenzo, Wallimann, Lea, Duru, Jens, Tringides, Christina M., Vörös, János, Ruff, Tobias
Format: Journal Article
Language:English
Published: England Elsevier B.V 01.08.2025
Subjects:
Activity-dependent slowing
agonists
Axonal conduction
axons
Axons - drug effects
Axons - physiology
Biosensing Techniques - instrumentation
biosensors
capsaicin
Capsaicin - pharmacology
Cells, Cultured
CMOS-based microelectrode array
Electrophysiological Phenomena
electrophysiology
Equipment Design
Human iPSC-derived sensory neurons
Humans
In vitro model
Induced Pluripotent Stem Cells - cytology
Microelectrodes
microstructure
Nociception
Nociceptors - cytology
Nociceptors - drug effects
Nociceptors - physiology
pain
PDMS microstructures
polydimethylsiloxane
sensory neurons
sowing
therapeutics
transient receptor potential vanilloid channels
TRPV Cation Channels - agonists
Nociception
Human iPSC-derived sensory neurons
Axonal conduction
CMOS-based microelectrode array
In vitro model
Activity-dependent slowing
PDMS microstructures
ISSN:0956-5663, 1873-4235, 1873-4235
Online Access:Get full text
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Summary:Neuropathic pain is characterized by aberrant activity of specific nociceptor populations, as demonstrated through functional assessments such as microneurography. Current treatments against severe forms of neuropathic pain demonstrate insufficient efficacy or lead to unwanted side effects as they fail to specifically target the affected nociceptors. Tools that can recapitulate aspects of microneurography in vitro would enable a more targeted compound screening. Therefore, we developed an in vitro platform combining a CMOS-based high-density microelectrode array with a polydimethylsiloxane (PDMS) guiding microstructure that captures the electrophysiological responses of individual axons. Human induced pluripotent stem cell-derived (hiPSC) sensory neurons were cultured in a way that allowed axons to be distributed through parallel 4 ×10μm microchannels exiting the seeding well before converging to a bigger axon-collecting channel. This configuration allowed the measurement of stimulation-induced responses of individual axons. Sensory neurons were found to exhibit a great diversity of electrophysiological response profiles that can be classified into different functional archetypes. Moreover, we show that some responses are affected by applying the TRPV1 agonist capsaicin. Overall, results using our platform demonstrate that we were able to distinguish individual axon responses, making the platform a promising tool for testing therapeutic candidates targeting particular sensory neuron subtypes. •Microfluidic platform on HD-MEA for recording hundreds of individually stimulated axons.•Axon conduction and excitability properties reveal distinct functional archetypes.•Distinct electrophysiological responses may correspond to neural subtypes.
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ISSN:0956-5663
1873-4235
1873-4235
DOI:10.1016/j.bios.2025.117418