Mutations in the voltage-gated sodium channels (Nav) 1.7, 1.8, and 1.9 are linked to human pain syndromes. Most of the mutations studied to date present with an intuitive pathomechanism, a direct link between the function of the channel and the phenotype of the patient. However, recent studies reported mutations that cause a gain of channel function but loss-of-pain in the patient, or the opposite: gain-of-pain in the patient but impaired channel function. For these mutations the underlying pathomechanism needs to be elucidated. In this study, we investigate the D1639N mutation of the SCN10A gene encoding Nav1.8, that has previously been described in a patient suffering from the chronic pain syndrome small fiber neuropathy (SFN). We used the neuroblastoma cell lines (ND7/23 and N1E115 cells) for whole cell patch-clamp experiments and immunofluorescence microscopy. We show that the amino acid substitution within in the channel leads to a significant reduction in current density, but does not alter any other tested biophysical gating properties of the channel (activation, fast and slow inactivation and recovery from fast inactivation). Thus, the D1639N mutation causes loss-of-function of the channel. Neither co-expression of ß-subunit 1 or 3, nor overnight incubation at lower temperature (27°C) rescued the current density. However, incubation with 1 mM lidocaine, but not 100 µM phenytoin, overnight restored the current density of Nav1.8/D1639N transfected cells. Ion channel blockers have been reported to support channel trafficking to the membrane by stabilizing trafficking deficient proteins, and thus the rescuing effect of lidocaine suggests a trafficking deficit of the D1639N mutation. Accordingly, we show enhanced protein levels in Nav1.8/D1639N injected oocytes (SDS Page). Nav1.8/D1639N transfected neuroblastoma cells harbor enhanced fluorescence intensity ratios when we compare the main cytoplasm with a small cytoplasmic hem near the nucleus. Thus, these enhanced amounts of protein likely accumulate in cell organelles in the cytoplasm, such as the endoplasmatic reticulum (ER). This relative fluorescence intensity is reduced after incubation with 1 mM lidocaine overnight, suggesting that lidocaine dissolves the accumulation of Nav1.8/D1639N and enhances trafficking to the membrane. According to our results, Nav1.8/D1639N is trafficking deficient. The accumulation of misfolded or trafficking deficient proteins in cell organelles in the cytoplasm, e.g. the ER, is known to possibly result in ER stress. ER stress is a relevant pathogenic factor in systemic diseases. Thus, the accumulation of Nav1.8/D1639N may result in ER stress causing the systemic disease SFN. Lidocaine could potentially be a suitable therapeutic option for this SFN patient carrying the D1639N mutation, and further clinical testing is needed.