Pocijepani SNAP-25 kao marker središnjeg mjesta djelovanja botulinum toksina tipa A na bol

master's thesis

• Title (english): Cleaved SNAP-25 as a marker of central site of Botulinum toxin Type A action on pain
• Author: Anna Ipša
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Hrvoje Rimac (član povjerenstva)
• Committee member: Ana Babić Perhoč (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Isprva samo smrtonosni toksin koji uzrokuje botulizam, BT-A se već više od 30 godina uspješno koristi u liječenju
različitih bolesti, od čega je kronična bol indikacija koja se i dalje istražuje.
Iako se smatra jednim od najpotentnijih bioloških toksina, pročišćeni farmakološki pripravak BT-A u nanomolarnim
dozama koristi se u liječenju različitih kliničkih stanja praćenih povećanom kontraktilnošću mišića. U pogledu liječenja
boli, velika mu je prednost što nakon jednokratne primjene njegovo djelovanje traje do nekoliko mjeseci, te tu dobiva
prednost nad poznatim analgeticima, naročito za liječenje kronične boli.
Dosadašnja istraživanja na modelima visceralne i bilateralne boli, u kojima je uočen bilateralni analgetski učinak BT-A
nakon unilateralne periferne i intratekalne, ali ne i središnje intracerebroventrikularne i intracisternalne primjene,
poslužili su kao temelj hipoteze o središnjemu segmentalnom analgetskom djelovanju BT-A na spinalnoj razini.
Imunohistokemijski detektiran pocijepani SNAP-25 u dorzalnome rogu kralješnične moždine
upućuje na retrogradni aksonalni transport s periferije do leđne moždine gdje onda ispoljava svoj antinociceptivni učinak
tako što modulira prijenos bolnog impulsa senzornim vlaknima na razini prve sinapse u leđnoj moždini.
Ovim radom se imunohistokemijski detektirao pocijepani SNAP-25 u dorzalnome rogu leđne moždine nakon periferne
primjene BT-A u desnu šapu štakora na karagenanskom modelu upalne boli. Nadalje, u skupini u kojoj je primijenjen
antitoksin (i.t.) uočena je statistički manja količina pocijepanog SNAP-25 proteina, što sugerira mogući transsinaptički
prelazak BT-A na razini leđne moždine. Ta saznanja svakako otvaraju prostor daljnjim istraživanjima o samome
mehanizmu transinaptičkog transporta BT-A.

Abstract (english)

At first merely a lethal toxin which causes botulism, BT-A has been successfully used for more than 30 years in the
treatment of various ailments, of which chronic pain is an indication that continues to be researched. Though considered
to be one of the most potent biological toxins, its purified pharmacological preparation BT-A in nanomolar doses is used
in treating various clinical conditions accompanied by augmented muscular contractility. With regard to pain treatment,
it offers a significant advantage – after a single administration, its effects persist for several months, which gives it an
edge over popular analgesics, especially for chronic pain treatment.
Previous research on visceral and bilateral pain models, which have shown a bilateral analgesic effect of BT-A after
unilateral peripheral and intrathecal, but not central intracerebroventricular and intracisternal administration, has served
as the foundation of the hypothesis on the central segmental analgesic effect of BT-A at the spinal level.
Immunohistochemically detected cleaved SNAP-25 in the dorsal horn of the spinal cord indicates a retrograde axonal
transport from the periphery to the spinal cord where it exhibits
its antinociceptive effect by modulating pain impulse transmission via sensory fibers at the level of the first synapse in
the spinal cord.
This paper has immunohistochemically detected cleaved SNAP-25 in the dorsal horn of the spinal cord after the
peripheral administration of BT-A in the right footpad of rats in the carrageenan-induced inflammation model.
Furthermore, the group in which the antitoxin was administered showed a statistically reduced amount of the cleaved
SNAP-25 protein, which suggests the possibility of the transsynaptic transfer of BT-A at the level of the spinal cord.
These observations invite further research into the transsynaptic transfer mechanism of BT-A.

• Keywords: botulinum toksin; bol; SNAP-25; spinalni segmenti; imunohistokemija
• Keywords (english): botulinum toxin; pain; SNAP-25; spinal segments; immunohystochemistry
• Language: croatian
• URN:NBN: urn:nbn:hr:163:059929
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2024-07-15
• Created on: 2022-07-26 15:11:04