IPSC-derived sensory neurons have evolved as innovative disease model of chronic neuropathic pain and offer a promising tool to improve the poor transferability of basic research findings in animal models to effective strategies for pain relief in humans.Several inherited pain disorders that cause spontaneous discharges of peripheral nerves as hallmark of neuropathic pain in humans and animal models also induce hyperexcitability of IPSC-derived sensory neurons. However, these mechanisms so far remain incompletely understood. Recent findings suggest that spontaneous activity in human DRG neurons from patients with neuropathic pain corresponds to characteristic electrophysiological alterations of membrane potential. Electrophysiological analysis of spontaneous activity in iPSC-derived sensory neurons suggest that similar electrophysiological alterations could underlie hyperexcitability of iPSC-derived sensory neurons from pain patients and are mostly absent in those of healthy probands that rarely show spontaneous activity.