Direct central nervous system effects of botulinum neurotoxin. (1st June 2018)

• Record Type: Journal Article
• Authors: Caleo, Matteo; Restani, Laura
• Is Part Of: Toxicon. Volume 147(2018)
• Page Start: 68
• Page End: 72
• Publication Date: 2018-06-01
• Subjects: Axonal transport -- Transcytosis -- SNAP-25 -- Motoneurons -- Spasticity -- Dystonia; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2017.10.027
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Local intramuscular injections of botulinum neurotoxin type A (BoNT/A) are effective in the treatment of focal dystonias, muscle spasms, and spasticity. However, not all clinical effects of BoNT/A may be explained by its action at peripheral nerve terminals. For example, the therapeutic benefit may exceed the duration of the peripheral neuroparalysis induced by the neurotoxin. In cellular and animal models, evidence demonstrates retrograde transport of catalytically active BoNT/A in projection neurons. This process of long-range trafficking is followed by transcytosis and action at second-order synapses. In humans, several physiological changes have been described following intramuscular delivery of BoNT/A. In particular, clinical studies have documented a decrease in Renshaw cell-mediated inhibition (i.e., recurrent inhibition), which may be important therapeutically for normalizing uncoordinated movements and overflow of muscle activity. In this review, we present data obtained in animal and experimental models that support direct central actions of BoNT/A mediated via retrograde axonal trafficking. We also discuss the reorganization of central circuitry induced by BoNT/A in patients, and the potential contribution of these effects to the therapeutic efficacy of the neurotoxin. Highlights: Not all therapeutic effects of BoNT/A in patients may be explained by local action at the NMJ. A significant proportion of BoNT/A undergoes retrograde transport following peripheral injection. Retrogradely transported BoNT/A may act on central circuits and directly contribute to clinical effects.