
pmid: 40215890
handle: 20.500.11850/731179
AbstractCurrent 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 - a specialized subclass of sensory neurons conveying potentially damaging stimuli information to the central nervous system. Neuropathic pain may involve different nociceptor subtypes in different patients. Tools that can distinguish nociceptive axons would enable a more targeted compound screening. Therefore, we developed anin vitroplatform combining a CMOS-based high-density microelectrode array with a polydimethylsiloxane (PDMS) guiding microstructure that captures the electrophysiological responses of nociceptors. Human induced pluripotent stem cell-derived (iPSC) nociceptors were cultured at low density with axons distributed through parallel 4 × 10 µm 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. Nociceptors 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 nociceptive axons from different subtypes. The platform provides a promising tool for screening potential candidates for nociceptor-specific drugs.
Nociception, Induced Pluripotent Stem Cells, Nociceptors, TRPV Cation Channels, Activity-dependent slowing, CMOS-based microelectrode array, Biosensing Techniques, Equipment Design, Axons, Electrophysiological Phenomena, Nociception; PDMS microstructures; Axonal conduction; Activity-dependent slowing; Human iPSC-derived sensory neurons; CMOS-based microelectrode array; In vitro model, In vitro model, Humans, PDMS microstructures, Capsaicin, Axonal conduction, Human iPSC-derived sensory neurons, Microelectrodes, Cells, Cultured
Nociception, Induced Pluripotent Stem Cells, Nociceptors, TRPV Cation Channels, Activity-dependent slowing, CMOS-based microelectrode array, Biosensing Techniques, Equipment Design, Axons, Electrophysiological Phenomena, Nociception; PDMS microstructures; Axonal conduction; Activity-dependent slowing; Human iPSC-derived sensory neurons; CMOS-based microelectrode array; In vitro model, In vitro model, Humans, PDMS microstructures, Capsaicin, Axonal conduction, Human iPSC-derived sensory neurons, Microelectrodes, Cells, Cultured
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