دورية أكاديمية
Analgesic effect of Botulinum toxin in neuropathic pain is sodium channel independent.
| العنوان: | Analgesic effect of Botulinum toxin in neuropathic pain is sodium channel independent. |
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| المؤلفون: | Kesdoğan AB; Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Scientific Center for Neuropathic Pain Research Aachen, SCN(Aachen), RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany., Neureiter A; Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany., Gaebler AJ; Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany., Kalia AK; Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany., Körner J; Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Department of Anesthesiology, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Department of Intensive and Intermediate Care, Medical Faculty, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Scientific Center for Neuropathic Pain Research Aachen, SCN(Aachen), RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany. Electronic address: jkoerner@ukaachen.de., Lampert A; Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Scientific Center for Neuropathic Pain Research Aachen, SCN(Aachen), RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany. |
| المصدر: | Neuropharmacology [Neuropharmacology] 2024 Aug 01; Vol. 253, pp. 109967. Date of Electronic Publication: 2024 Apr 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Pergamon Press Original Publication: Oxford, New York, Pergamon. |
| مواضيع طبية MeSH: | Neuralgia*/drug therapy , Botulinum Toxins, Type A*/pharmacology , Botulinum Toxins, Type A*/therapeutic use , Induced Pluripotent Stem Cells*/drug effects , NAV1.7 Voltage-Gated Sodium Channel*/genetics , NAV1.7 Voltage-Gated Sodium Channel*/metabolism, Humans ; Analgesics/pharmacology ; Animals ; NAV1.3 Voltage-Gated Sodium Channel/genetics ; Sensory Receptor Cells/drug effects ; Sensory Receptor Cells/metabolism ; HEK293 Cells ; Cell Line |
| مستخلص: | Botulinum neurotoxin type A BoNT/A is used off-label as a third line therapy for neuropathic pain. However, the mechanism of action remains unclear. In recent years, the role of voltage-gated sodium channels (Nav) in neuropathic pain became evident and it was suggested that block of sodium channels by BoNT/A would contribute to its analgesic effect. We assessed sodium channel function in the presence of BoNT/A in heterologously expressed Nav1.7, Nav1.3, and the neuronal cell line ND7/23 by high throughput automated and manual patch-clamp. We used both the full protein and the isolated catalytic light chain LC/A for acute or long-term extracellular or intracellular exposure. To assess the toxin's effect in a human cellular system, we differentiated induced pluripotent stem cells (iPSC) into sensory neurons from a healthy control and a patient suffering from a hereditary neuropathic pain syndrome (inherited erythromelalgia) carrying the Nav1.7/p.Q875E-mutation and carried out multielectrode-array measurements. Both BoNT/A and the isolated catalytic light chain LC/A showed limited effects in heterologous expression systems and the neuronal cell line ND7/23. Spontaneous activity in iPSC derived sensory neurons remained unaltered upon BoNT/A exposure both in neurons from the healthy control and the mutation carrying patient. BoNT/A may not specifically be beneficial in pain syndromes linked to sodium channel variants. The favorable effects of BoNT/A in neuropathic pain are likely based on mechanisms other than sodium channel blockage and new approaches to understand BoNT/A's therapeutic effects are necessary. Competing Interests: Declaration of competing interest A.L. has an unrelated research agreement with Grunenthal and had an unrelated research agreement with Hoffmann-La Roche. A.L. receives counseling fees from Grunenthal. A.K.K is currently employed by Grunenthal. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| المشرفين على المادة: | 0 (SCN9A protein, human) |
| تواريخ الأحداث: | Date Created: 20240424 Date Completed: 20240518 Latest Revision: 20240518 |
| رمز التحديث: | 20240519 |
| DOI: | 10.1016/j.neuropharm.2024.109967 |
| PMID: | 38657946 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-7064 |
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| DOI: | 10.1016/j.neuropharm.2024.109967 |