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

Aylin B Kesdoğan; Anika Neureiter; Arnim J Gaebler; Anil K Kalia; Jannis Körner; Angelika Lampert

doi:10.1016/j.neuropharm.2024.109967

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

Neuropharmacology. 2024 Apr 23:253:109967. doi: 10.1016/j.neuropharm.2024.109967. Online ahead of print.

Authors

Aylin B Kesdoğan¹, Anika Neureiter², Arnim J Gaebler³, Anil K Kalia², Jannis Körner⁴, Angelika Lampert¹

Affiliations

¹ 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.
² Institute of Neurophysiology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany.
³ 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.
⁴ 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.

PMID: 38657946
DOI: 10.1016/j.neuropharm.2024.109967

Abstract

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.