Naslov
COMPLEX MECHANISMS OF BOTULINUM TOXIN TYPE A ACTION ON EXPERIMENTAL PAIN -TIME TO LOOK BEYOND THE FIRST SYNAPSE

Autori
Mustapić Matej, Skenderović Marijana, Vađunec Dalia, Bach-Rojecky Lidija

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

Izvornik
Pahrmaca 2022. 52 Suppl 2: 1-236 / - , 2022, 221-221

Skup
10. hrvatski kongres farmakologije i 1. hrvatski kongres kliničke farmakologije s međunarodnim sudjelovanjem

Mjesto i datum
Opatija, Hrvatska, 22.09.2022. - 25.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Recenziran

Ključne riječi
pain, botulinum toxin type A, transcytosis

Sažetak
INTRODUCTION: Botulinum neurotoxin type A (BoNT-A) cleaves SNAP-25, a part of cellular machinery that mediates neurotransmitters exocytosis. Its antinociceptive effect, demonstrated in various experimental pain models, is mediated by complex mechanisms in the central nervous system, possibly at the level of the first synapse. This study aimed to investigate possible transcytosis of BoNT/A after its peripheral application. MATERIALS AND METHODS: BoNT-A (7 IU/kg) was unilaterally applied in the facial vibrissae of Wistar rats one day before intracisternal administration of antitoxin against BoNT-A (5 IU/10µL). After seven days, formalin (2.5%) was injected into both facial vibrissae. The time rats spent rubbing the application sites was measured for 45 minutes. Immunohistochemical analyses of c-Fos (a marker of neural activation) and cleaved SNAP-25 (a marker of BoNT-A activity) were performed in the sections of the trigeminal nucleus caudalis (TNC). Experiments were approved by the Ethical Committee of the University of Zagreb School of Medicine. RESULTS: Peripheral application of BoNT-A reduced the time that rats spent rubbing the injected area, while antitoxin prevented this effect. Immunohistochemical data showed that BoNT-A reduced the expression of c-Fos positive neurons at the ipsilateral side of TNC and, to a lesser extent, on the contralateral side, while the applied antitoxin significantly reduced this effect. Similarly, antitoxin reduced the BoNT-A associated expression of cleaved SNAP-25 at both sides of the TNC. CONCLUSIONS: Here we show that BoNT-A decreases the pain intensity, especially at the beginning of the inflammatory phase, and suggest its possible transcytosis within TNC in the brainstem. This research is supported by Croatian Science Foundation (project no. HRZZ-UIP-2019-04- 8277).

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

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