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.<\/p>\n
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\u2019s 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 multi electrode array measurements.<\/p>\n
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.<\/p>\n
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\u2019s therapeutic effects are necessary.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,53,76],"therapeutic_areas":[56,143],"target_categories":[61],"target_families":[332],"targets":[116,236],"resource_keyword":[],"class_list":["post-14263","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-drug-discovery","therapeutic_areas-pain","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-7","targets-nav1-3"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/14263","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=14263"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=14263"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=14263"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=14263"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=14263"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=14263"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=14263"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=14263"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=14263"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}