Abstract：
BACKGROUND AND PURPOSE:Botulinum toxin type A (BoNT/A) injections into hyperactive muscles provide effective treatment for spasticity and dystonias, presumably due to its local effects on extrafusal and intrafusal motor fibres. A recent discovery of toxin's retrograde axonal transport to CNS might suggest additional action sites. However, in comparison to cholinergic peripheral terminals, functional consequences of BoNT/A direct central action on abnormally increased muscle tone are presently unknown. To address this question, the central effects of BoNT/A were assessed in experimental local spastic paralysis. EXPERIMENTAL APPROACH:Local spastic paralysis was induced by injection of tetanus toxin (1.5 ng) into rat gastrocnemius. Subsequently, BoNT/A (5 U·kg-1 ) was applied i.m. into the spastic muscle or intraneurally (i.n.) into the sciatic nerve to mimic the action of axonally transported toxin. Functional role of BoNT/A transcytosis in spinal cord was evaluated by lumbar i.t. application of BoNT/A-neutralizing antitoxin. BoNT/A effects were studied by behavioural motor assessment and cleaved synaptosomal-associated protein 25 (SNAP-25) immunohistochemistry. KEY RESULTS:Tetanus toxin evoked muscular spasm (sustained rigid hind paw extension and resistance to passive ankle flexion). Subsequent injections of BoNT/A, i.m. or i.n, reduced tetanus toxin-evoked spastic paralysis. Beneficial effects of i.n. BoNT/A and occurrence of cleaved SNAP-25 in ventral horn were prevented by i.t. antitoxin. CONCLUSIONS AND IMPLICATIONS:Axonally transported BoNT/A relieves muscle hypertonia induced by tetanus toxin, following the trans-synaptic movement of BoNT/A in the CNS. These results suggest that such direct, centrally mediated reduction of abnormal muscle tone might contribute to the effectiveness of BoNT/A in spasticity and hyperkinetic movement disorders.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Matak Idoi
10.1111/bph.14846subject
Has Abstractpub_date
2020-01-01 00:00:00pages
65-76issue
1eissn
0007-1188issn
1476-5381journal_volume
177pub_type
杂志文章abstract：:The vanilloid receptor (VR1) is a ligand-gated ion channel, which plays an important role in nociceptive processing. Therefore, a pharmacological characterization of the recently cloned rat VR1 (rVR1) was undertaken. HEK293 cells stable expressing rVR1 (rVR1-HEK293) were loaded with Fluo-3AM and then incubated at 25 d...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0703390
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doi：10.1111/j.1476-5381.1987.tb11287.x
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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