Ekspresija enkefalina u kralježničnoj moždini u modelu neuropatske boli

master's thesis

• Title (english): Expression of enkephalins in spinal cord in model of neuropathic pain
• Author: Petra Čarapina
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Iva Mucalo (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: 2016-07-19, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Kompleksna patofiziologija neuropatske boli uključuje brojne mehanizme na perifernoj, spinalnoj i supraspinalnoj razini koji su posredovani važnim neurotransmitorima poput glutamata, GABA-e, glicina te transmembranskim proteinima kao što su N tip Ca2+ kanala, TRPV1 vaniloidni receptori te opioidni μ-, δ- i κ-receptori. Brojnim je istraživanjima pokazana značajna uloga endogenog opioidnog sustava u procesima transmisije i modulacije boli. Eksprimetalni modeli neuropatske boli pokazuju povećanje aktivnosti endogenog opioidnog sustava, a upravo enkefalini imaju najviše dokaza o učinkovitosti na spinalnoj razini. Međutim, u stanjima neuropatske boli koja je kroničnog trajanja, uloga endogenog opioidnog sustava može biti značajno promijenjena. Analgetski učinak BT-A je do danas pokazan u brojnim pretkliničkim i kliničkim studijama, u kojima BT-A pokazuje bitnu razliku u odnosu na ostale analgetike, a to je da dugotrajno (višemjesečno) smanjuje bol nakon jednokratne lokalne primjene malih doza. U ovom je diplomskom radu imunohistokemijskom metodom mjerena površina i intenzitet imunoreaktivnosti enkefalina u uzorcima tkiva dorzalnog roga kralježnične moždine triju skupina životinja; kontrole, životinja s neuropatijom izazvanom parcijalnom transekcijom n. ishiadicusa te životinja s neuropatijom kojima je injiciran BT-A u plantarnu površinu stražnje desne šape. Pokazali smo obostran porast površine i intenziteta imunoreaktivnosti kod skupine životinja kojoj je injiciran BT-A u odnosu na kontrolu i na skupinu životinja s neuropatijom. Temeljem toga možemo pretpostaviti da BT-A posredno povećava aktivnost endogenog opioidnog sustava povećanjem sinteze endogenih opioida, točnije enkefalina. Potrebna su daljnja istraživanja povezanosti endogenog opioidnog sustava i antinociceptivnog djelovanja BT-A kako bi se rasvijetlio središnji mehanizam djelovanja BT-A i usmjerila njegova klinička primjena kao potencijalne nove terapijske opcije u liječenju neuropatske boli.

Abstract (english)

Complex pathophysiology of neuropathic pain involves various mechanisms on peripheral, spinal and supraspinal levels which are mediated by important neurotransmitters such as glutamate, GABA, glycine and transmembrane proteins like N-type calcium channels, TRPV1 vaniloid receptors and opioid μ-, δ- and κ-receptors.
Numerous research has shown a significant role endogenous opioid system has in processes of transmission and modulation of pain. Experimental models of neuropathic pain show the enhacement of the activity of endogenous opioid system, and vast majority of envidence for the involment in the regulation of nociceptive processes on the spinal level has been found for enkephalins. However, in conditions like neuropathic pain, which is of chronic duration, the role of the opioid system can be notably altered.
Analgetic effect of BT-A has been demonstrated in numerous preclinical and clinical studies in which BT-A significantly differs from other analgetics in terms that decreases pain for a long-term period (several months) after single local injection of small doses.
In this work was measured enkephalin immunoreactivity by immunohistochemical methods in tissue samples of the dorsal horn of the spinal cord of three groups of animals; control animals, animals with neuropathic pain induced by partial transection of n. ishiadicus and animals with neuropathic pain which were injected with BT-A into the plantar surface of the hindpaw. We have shown bilateral increase in surface and intensity of immunoreactivity in group of animals which were injected with BT-A in comparison with control animals and animals with neuropathic pain. Taking everything into account, we can assume that BT-A indirectly increases the activty of endogenous opioid system by up-regulation of enkephalin synthesis.
Further investigation which aim to correlate endogenous opioid system and antinociceptive effect of BT-A is needed in order to elucidate the central mechanism of action of BT-A and also in order to direct its clinical application as a new therapeutic option in treatment of neurophatic pain.

• Keywords: enkefalini; neuropatska bol; botulinum toksin tipa A
• Keywords (english): enkephalins; neurophatic pain; botulinum toxin type A
• Language: croatian
• URN:NBN: urn:nbn:hr:163:108290
• 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: Access restricted to students and staff of home institution
• Created on: 2016-11-30 16:47:57