SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing

Kist, Andreas M.; Dagrun, Sagafos; Rush, Anthony M.; Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Luisa, Kaluza; Meents, Jannis; Zhang, Zhiping; Carr, T. Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Lampert, Angelika; Namer, Barbara

doi:10.1371/journal.pone.0161789

Cited by 38 publications

(33 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, the characteristic pronounced activity-dependent slowing of conduction in silent nociceptors (Serra et al, 1999;Weidner et al, 1999) has been linked to increased sodium influx via Na V 1.8 based on modeling results Tigerholm et al, 2014). This suggestion was supported recently in a patient with Na V 1.8 mutation who revealed increased activity-dependent slowing patterns in silent nociceptors (Kist et al, 2016).…”

Section: Ttx Effects (Pig In Vivo )mentioning

confidence: 80%

TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors

Jonas

Prato

Lechner

et al. 2020

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

Pronounced activity-dependent slowing of conduction has been used to characterize mechano-insensitive, "silent" nociceptors and might be due to high expression of Na V 1.8 and could, therefore, be characterized by their tetrodotoxin-resistance (TTX-r). Nociceptor-class specific differences in action potential characteristics were studied by: (i) in vitro calcium imaging in single porcine nerve growth factor (NGF)-responsive neurites; (ii) in vivo extracellular recordings in functionally identified porcine silent nociceptors; and (iii) in vitro patch-clamp recordings from murine silent nociceptors, genetically defined by nicotinic acetylcholine receptor subunit alpha-3 (CHRNA3) expression. Porcine TTX-r neurites (n = 26) in vitro had more than twice as high calcium transients per action potential as compared to TTX-s neurites (n = 18). In pig skin, silent nociceptors (n = 14) characterized by pronounced activity-dependent slowing of conduction were found to be TTX-r, whereas polymodal nociceptors were TTX-s (n = 12) and had only moderate slowing. Mechano-insensitive cold nociceptors were also TTX-r but showed less activity-dependent slowing than polymodal nociceptors. Action potentials in murine silent nociceptors differed from putative polymodal nociceptors by longer duration and higher peak amplitudes. Longer duration AP in silent murine nociceptors linked to increased sodium load would be compatible with a pronounced activity-dependent slowing in pig silent nociceptors and longer AP durations could be in line with increased calcium transients per action potential observed in vitro in TTX-resistant NGF responsive porcine neurites. Even though there is no direct link between slowing and TTX-resistant channels, the results indicate that axons of silent nociceptors not only differ in their receptive but also in their axonal properties.

show abstract

Section: Ttx Effects (Pig In Vivo )mentioning

confidence: 80%

TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors

Jonas

Prato

Lechner

et al. 2020

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several variants have been reported without functional testing . Recently, a Na v 1.8 variant has been linked to a syndrome with clinical characteristics similar to IEM …”

Section: Epidemiologymentioning

confidence: 99%

“…203,204 Recently, a Na v 1.8 variant has been linked to a syndrome with clinical characteristics similar to IEM. 205 2.10.2 | Na V 1.7 in PEPD PEPD, previously known as familial rectal pain (OMIM 167400), is an inherited condition characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. Patients with PEPD can also suffer from autonomic dysfunction leading to poor feeding and reflux, vomiting, tonic attacks, breath holding spells, and bradycardia that sometimes requires insertion of a pacemaker.…”

Section: Voltage-gated Sodium Channelopathies In Sfnmentioning

confidence: 99%

Small‐fiber neuropathy: Expanding the clinical pain universe

Sopacua

Hoeijmakers

Merkies

et al. 2019

J Peripheral Nervous Sys

View full text Add to dashboard Cite

Small‐fiber neuropathy (SFN) is a disorder of thinly myelinated Aδ and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life. According to international criteria, the diagnosis is established by the assessment of intraepidermal nerve fiber density and/or quantitative sensory testing. SFN is mainly associated with autoimmune diseases, sodium channel gene variants, diabetes mellitus, and vitamin B12 deficiencies, although in more than one half of patients no etiology can be identified. Recently, gain‐of‐function variants in the genes encoding for the Nav1.7, Nav1.8 and Nav1.9 sodium channel subunits have been discovered in SFN patients, enlarging the spectrum of underlying conditions. Sodium channel gene variants associated with SFN can lead to a diversity of phenotypes, including different pain distributions and presence or absence of autonomic symptoms. This suggests that SFN is part of a clinical continuum. New assessments might contribute to a better understanding of the cellular and molecular substrates of SFN and might provide improved diagnostic methods and trial designs in the future. Identification of the underlying mechanisms may inform the development of drugs that more effectively address neuropathic pain and autonomic symptoms of SFN.

show abstract

“…Calcium-imaging studies indirectly show activation of the sensory neurons via increased free intracellular calcium levels. Electrophysiological recordings of C fibers have been performed in humans via microneurography 170 in complex regional pain syndrome, 171 erythromelalgia-like symptoms, 172,173 and other neuropathies. Microneurography has been suggested for potential use as a biomarker for pain, and these recordings could be performed in patients with SCD.…”

Section: Measures Of Underlying Pain Mechanisms: Pain/ Vaso-occlusivementioning

confidence: 99%

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

Farrell

Panepinto

Carroll³

et al. 2019

Blood Advances

View full text Add to dashboard Cite

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

show abstract

SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing

Cited by 38 publications

References 45 publications

TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors

TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors

Small‐fiber neuropathy: Expanding the clinical pain universe

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

Contact Info

Product

Resources

About