Neuropathic pain may be linked to mutations in the voltage gated sodium channel (Nav) subtype Nav1.7 encoded by the SCN9A gene. Interestingly, 13% of the Caucasian population harbor the Nav1.7/R1150W polymorphism, which may render the carrier more prone to develop chronic pain. The impact of this variant on nociceptor excitability is still unclear and only a fraction of carriers with p.R1150W develops severe pain symptoms during their lifetime, such as small fiber neuropathy (SFN). The onset of SFN can be correlated with a reduction of intraepidermal small nerve fibers in subgroups of SFN patients (Cazzato et al., 2017), which seems contra intuitive to the chronic pain syndrome these patients suffer from. The specific genetic background of the expressing cells may play a crucial role and needs further investigation. Here, we investigated human stem cell derived nociceptors of a SFN patient carrying the Nav1.7/R1150W polymorphism. Skin biopsies showed a decrease of intraepidermal nerve fiber density and an elongation of the dermal nodes of Ranvier. We reprogrammed the patient’s fibroblasts carrying Nav1.7/R1150W into induced pluripotent stem cells (iPS cells) and differentiated them into nociceptors using an optimized protocol (Eberhardt et al., 2015 based on Chambers et al., 2012). To investigate the pathophysiological relevance of the patient-specific genetic background, we performed calcium-imaging, patch-clamp analysis and multi-electrode recordings to assess the impact of the genetic variant on cellular excitability of the human nociceptors. With these experiments, we aim to study the pathophysiological basis of this pain syndrome. Individual in vitro testing for the efficacy of analgesic might help to translate these findings back to the patient offering the potential for personalized therapy.