p.L1612P, a novel voltage-gated sodium channel Nav1.7 mutation inducing a cold sensitive paroxysmal extreme pain disorder.

Détails

ID Serval
serval:BIB_3302716943FA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
p.L1612P, a novel voltage-gated sodium channel Nav1.7 mutation inducing a cold sensitive paroxysmal extreme pain disorder.
Périodique
Anesthesiology
Auteur(s)
Suter M.R., Bhuiyan Z.A., Laedermann C.J., Kuntzer T., Schaller M., Stauffacher M.W., Roulet E., Abriel H., Decosterd I., Wider C.
ISSN
1528-1175 (Electronic)
ISSN-L
0003-3022
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
122
Numéro
2
Pages
414-423
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BACKGROUND: Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation.
METHODS: Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature.
RESULTS: The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady-state inactivation curve (V1/2 from -61.8 ± 4.5 mV to -30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady-state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit.
CONCLUSIONS: The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.
Mots-clé
Adolescent, Adult, Amitriptyline/pharmacology, Antidepressive Agents, Tricyclic/pharmacology, Cell Line, Child, Cold Temperature, DNA/genetics, Female, Humans, Male, Middle Aged, Mutation/genetics, NAV1.7 Voltage-Gated Sodium Channel/genetics, NAV1.7 Voltage-Gated Sodium Channel/metabolism, Patch-Clamp Techniques, Pedigree, Plasmids, Somatoform Disorders/genetics
Pubmed
Web of science
Création de la notice
10/02/2015 14:03
Dernière modification de la notice
20/08/2019 14:18
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