Functional assays using human induced pluripotent stem cell (hiPSC)-derived sensory neurons are expected to predict the drug safety and side effects in human peripheral nervous system. However, evaluation assays in hiPSC-derived sensory neurons has not been established, and electrophysiological response to pain-related molecules are not known. In this study, we aimed to evaluate the physiological responses to pain-related molecules including anti-cancer drugs in cultured hiPSC-derived sensory neurons using high-throughput multi-electrode array (MEA) system. In capsaicin, menthol, and AITC administration, evoked responses depending on TPRV1, TRPM8, and TRPA1 channel were detected, respectively. We found that hiPSC-derived sensory neurons are a heterogeneous cell population that have different responses to temperature and pain molecules, like living body. Cold hypersensitivity responses were also detected in concentration dependent manner of anti-cancer drug oxaliplatin. These results indicated that this MEA evaluation method using human iPSC-derived sensory neurons is effective as a pain-related toxicity in human peripheral nervous system.

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