Analgesic effect of Botulinum toxin in neuropathic pain is sodium channel independent.

Autor: 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.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2024 Aug 01; Vol. 253, pp. 109967. Date of Electronic Publication: 2024 Apr 23.
DOI: 10.1016/j.neuropharm.2024.109967
Abstrakt: 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.)
Databáze: MEDLINE
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