In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array

Area of Science:

• Neuroscience
• Stem Cell Biology
• Pharmacology

Background:

• Drug-induced peripheral neuropathy is a common chemotherapy side effect.
• Accurate assessment methods for compound-induced neuropathy and pain are lacking.
• Human-induced pluripotent stem cell (hiPSC)-derived sensory neurons offer a promising, animal-free alternative for human extrapolation.

Purpose of the Study:

• To evaluate the response of hiPSC-derived sensory neurons to pain-related compounds using in vitro microelectrode array (MEA) measurements.
• To assess the potential of this system to model drug-induced neuropathy, specifically oxaliplatin-induced cold sensitivity.

Main Methods:

• Cultured hiPSC-derived sensory neurons were analyzed for gene expression of key pain channels (Nav1.7, TRPV1, TRPA1, TRPM8).
• Neural activity responses to specific agonists (capsaicin, AITC, menthol) and temperature changes were measured using MEA.
• The effect of oxaliplatin on neuronal response to AITC was evaluated to model cold sensitivity.

Main Results:

• Sensory neurons expressed typical pain-related ion channels.
• Evoked responses to channel-specific agonists and temperature variations were successfully detected.
• Oxaliplatin exposure enhanced neuronal response to AITC in a concentration-dependent manner, mimicking increased cold sensitivity.

Conclusions:

• The in vitro MEA system using hiPSC-derived sensory neurons is a viable alternative to animal testing for evaluating compound-induced peripheral neuropathy and pain.
• This model can successfully reproduce specific drug-induced sensory alterations like oxaliplatin's effect on cold sensitivity.
• This approach holds significant potential for advancing the safety assessment of new chemical entities and pharmaceuticals.