Peripheral paresthesia caused by mutation in the gene SCN10A

The neurons of dorsal root ganglia are an important part of the somatosensory system. They detect various stimuli such as temperature, touch or painful cues, translate them into action potentials and transmit the information along afferent pathways to the central nervous system. The voltage-gated sodium channel NaV1.8 is crucial for the electrical signaling of sensory neurons and several mutations in the associated gene SCN10A have been associated with neuropathic pain and itch in humans, primarily affecting the body periphery.

Scientists at the "Center of Brain, Behavior and Metabolism" (CBBM) at the University of Lübeck, together with colleagues at the University Hospital Aachen, have now identified a mutation (p.V1287I) in the SCN10A gene causing a temperature regulation disorder involving hands and feet. Using patch-clamp electrophysiology, the researchers showed that the mutation confers both gain-of-function and loss-of-function properties to NaV1.8 and renders sensory neurons hyperexcitable. The study demonstrates that nonpainful peripheral paresthesia should be considered part of the clinical spectrum of NaV1.8-associated disorders.

The study was funded by the DFG (LE-2338-2).

Contact: Prof. Dr. Enrico Leipold, CBBM & Department of Anesthesiology and Intensive Care, Ratzeburger Allee 160, 23562 Luebeck, Phone: +49 3101 8610, enrico.leipold(at)


Loose S, Lischka A, Kuehs S, Nau C, Heinemann SH, Kurth I, Leipold E. Peripheral temperature dysregulation associated with functionally altered NaV1.8 channels. Pflugers Arch. 2023 Sep 11. doi: 10.1007/s00424-023-02856-2. Epub ahead of print. PMID: 37695396.


Cardiac defect in rare genetic disease unraveled

It is well established that high levels of thyroid hormone cause elevated heart rate. However, patients with a mutation in their thyroid hormone receptor are surprisingly resistant against this effect. Researchers of the Institute of Endocrinology and Diabetes at the “Center of Brain Behavior and Metabolism” (CBBM) have now unraveled the underlying molecular mechanism in the corresponding animal model.

„We learnt from our colleagues in Cambridge that their patients with a mutation in thyroid hormone receptor alpha, which they routinely treat with high doses of thyroxine, did not respond with elevated heart rate”, elaborates Prof Jens Mittag, leader of the study published in the prestigious journal “Nature Communications”. “We were able to replicate this finding in our corresponding animal model, which allowed us in depth studies. These studies revealed that the heart has a defect due to the mutation, which arises already during embryonal development. As a consequence, several cardiac ion channels are no longer regulated by thyroid hormone leading to the observed resistance.”

„Most interestingly, the regulation of two important pacemaker channels is still intact in the animals, which demonstrates that these channels are not the sufficient to elevate heart rate”, adds Dr. Riccardo Dore, first author of the study. “Given that current textbooks assign the elevated heart rate in hyperthyroidism to these two channels, this aspect of cardiac thyroid hormone action needs to be rewritten.”

The published study is part of the DFG-funded Transregio SFB 296 „Local Control of Thyroid Hormone Action (LocoTact)“, which started in 2020 and includes in addition to the University of Lübeck also the Universitätsklinikum Duisburg-Essen and the Charité Berlin.

Contact Information: Prof. Dr. Jens Mittag, CBBM, Institut für Endokrinologie & Diabetes, AG Molekulare Endokrinologie, Jens.Mittag(at), +49 451 3101 7826, Webpage: