Utjecaj botulinum toksina tipa A na aktivaciju neurona u talamusu u modelu upalne boli

master's thesis

• Title (english): The effect of botulinum toxin type A on c-Fos activation in thalamus in inflammatory pain model
• Author: Ena Bulović
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Višnja Drinovac (član povjerenstva)
• Committee member: Ivan Pepić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2017-09-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Kliničkim i pretkliničkim studijama pokazano je da jednokratno lokalno primijenjen BT-A smanjuje bol tijekom nekoliko mjeseci, što se smatra velikom prednosti u odnosu na danas dostupne analgetike. Brojnim eksperimentalnim istraživanja na animalnim i ljudskim modelima boli potvrđen je analgetski učinak BT-A. Međutim, za razliku od poznatog miorelaksirajućeg mehanizma djelovanja, mehanizam djelovanja botulinum toksina na bol još uvijek je nepoznat. Novija ispitivanja vode prema zaključcima da BT-A antinociceptivno djeluje na razini središnjeg živčanog sustava, a ne periferno kako se ranije smatralo. Prema tome, cilj ovog rada bio je odrediti mjesto centralnog djelovanja botulinum toksina praćenjem aktivacije c-Fos proteina kao prihvaćenog markera aktivacije neurona uslijed boli. Hipoteza rada je bila da BT-A analgetski učinak ostvaruje na spinalnoj razini. Ispitivanja su provedena na tkivu mozga mužjaka štakora soja Wistar kojima je prethodno uzrokovana bol formalinom. BT-A je primijenjen u moždane komore (i.c.v.) u dozi od 1 i.j./kg. Kontrolnoj skupini je umjesto BT-A i.c.v. primijenjena fiziološka otopina (0,9 % NaCl). Rezultati kvantifikacije c-Fos imunoreaktivnosti u talamusu su pokazali da periferno injiciranje formalina dovodi do aktivacije neurona u toj regiji mozga, što je u skladu s očekivanjima i rezultatima ranijih ispitivanja. Međutim, BT-A primijenjen u moždane komore nije smanjio broj c-Fos pozitivnih neurona. Ovi rezultati su još jedan od dokaza koji potvrđuju hipotezu o segmentalnom antinociceptivnom djelovanju BT-A na razini kralježnične moždine i isključuju više centre, te dodatno doprinose rasvjetljavanju mjesta djelovanja BT-A u središnjem živčanom sustavu.

Abstract (english)

Clinical and preclinical trials have shown that BT-A decreases pain for several monhs after single local injection, which is a big advantage in comparison to today availiable analgetics. Numerous research on animal and human pain models have confirmed these findings. Unlike relatively established myorelaxant mechanism of botulinum toxin, antinociceptive mechanism still remains unknown. Novel research conclude that the antinociceptive effects of botulinum toxin are of central and not, as it was earlier considered, peripheral origin. The goal of this experiment was to establish the exact location of BT-A activity in central nervous system. Hypothesis is that BT-A accomplishes analgetic effects on spinal level. Male Wistar rats were injected i.c.v. with BT-A (1 i.u./kg). The control group rats were. injected i.c.v. with physiological saline (0,9 % NaCl) instead of BT-A. The animals were sacrificed after the formalin test and the brain samples were collected, processed and used for immunohistochemical analysis. The results for experimental and control group were obtained after counting the number of c-Fos positive neurons. The average number of c-Fos positive neurons was greater for the control group. Based on the results it is concluded that BT-A fails to show effectiveness after i.c.v. application and that the analgetic effect is of spinal, and not supraspinal origin. Further research is needed to investigate mechanism of BT-A antinociceptive activity in spinal cord.

• Keywords: botulinum toksin; bol; c-Fos; formalinski test; imunohistokemija
• Keywords (english): botulinum toxin; pain; c-Fos; formalin test; immunohistochemistry
• Language: croatian
• URN:NBN: urn:nbn:hr:163:736846
• 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: Open access
• Created on: 2021-04-19 13:40:17