Naslov
CENTRAL EFFECTS OF BOTULINUM TOXIN-TYPE A

Autori
Lacković, Zdravko ; Bach-Rojecky, Lidija ; Matak, Ivica ; Filipović, Boris ;

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts: The 42nd International Danube Neurology Symposium October 21 - 23, 2010, Zagreb CD / Vida Demarin - Zagreb, 2010, CD-CD

Skup
The 42nd International Danube Neurology Symposium October 21 - 23, 2010, Zagreb

Mjesto i datum
Zagreb, Hrvatska, 21.10.2010. - 23.10.2010

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Nije recenziran

Ključne riječi
botulinum toxin; pain; axonal transport; n. trigeminus
(botulinum toksin; bol; aksonalni transport; n.trigeminus)

Sažetak
Early studies with radioactively labelled botulinum toxin A (BTX-A) reported the axonal transport within peripheral nerves to spinal dorsal horn (Habermann, Naunyn-Schmiedeberg’s Arch Pharmac. 281 ; 1974:47, Wiegand et al., Naunyn Schmiedebergs Arch Pharmac 292 ; 1976:161), but remained forgotten and were not reproduced in one later study (Tang Liu et al., Toxicon 42 ; 2003:461). Also, the main objections to these early studies were the inability to assess the character of this radioactivity and possible enzymatic activity of axonally transported BTX-A. Many reports on central effects of BTX-A after BTX-A peripheral application came from preclinical and clinical studies with spinal cord reflexes and cortical excitability. Series of studies (Moreno-Lopez et al., Neuroscience. 81 ; 1997:437 , Neuroscience. 81 ; 1997:457) with cat abducens motoneurons showed that increased doses of BTX-A applied into the lateral rectus lead to decrease of motoneuronal discharge and central synaptic alterations, which could not be attributed to indirect central effects resulting from neuromuscular junction blockade and paralysis which is complete even at low doses. More recently after peripheral injection of high doses of BTX-A its enzymatic activity, ie. cleavage of SNAP-25 was found in the CNS, as well as indications of BTX transcytosis (Antonucci F, at al J. Neurosci. 28: 3689-3696. These studies indicated the possibility that high doses of BTX-A could be axonally transported to the CNS. Currently prevailing opinion on mechanism of BTX-A antinociceptive activity is analogous to its peripheral activity on neuromuscular junction (Cui et al., Pain. 107: 2004:125). However, study on model of bilateral muscular hyperalgesia (Bach-Rojecky & Lacković, Pharmacol Biochem Behav. 94 ; 2009:234) excluded the involvement of peripheral nerve endings in reduction of pain, especially the pain contralateral to BTX-A application. Moreover, pharmacological inhibition of axonal transport in peripheral nerve completely abolished the antinociceptive effects, and demonstrated the functional significance of axonal transport of BTX-A-low doses. In project continuation, using anti-cleaved SNAP-25 antibody we studied the effect of low antinociceptive doses of BTX-A on SNAP-25 cleavage in the central sensory nuclei. First results will be presented. Antinociceptive effect of BTX A is only clearly known central action of peripherally administered toxin. On the other hand the existence of axonal transport and even more of transynaptic transport opens numerous new possibilities. Anti-BTX-A-cleaved SNAP-25 antibody was a kind gift from prof. Ornella Rossetto, University of Padua, Italy. Supported by Croatian Ministry of Education, Science and Sport, and Deutscher Akademischer Austausch Dienst (DAAD)

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA