Role of enkephalins in experimental inflammatory pain

master's thesis

• Title: Uloga enkefalina u eksperimentalnoj upalnoj boli
• Author: Mirna Momčilović
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky
• Committee member: Sanda Vladimir-Knežević
• Committee member: Ana Mornar Turk
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2015-12-18, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Upalna bol nastaje kao posljedica upale ili ozljede tkiva prilikom čega dolazi do lučenja različitih upalnih medijatora koji djeluju izravno aktivirajući nociceptore ili interferiraju sa signalnim procesima unutar njih. Tijekom učestalog izbijanja primarnih neurona pri upali dolazi do brojnih promjena u SŽS-u, praćenih pojavama poput senzitizacije, hiperalgezije i alodinije. Brojna istraživanja su pokazala značajnu ulogu endogenog opioidnog sustava u procesima transmisije i modulacije bolne informacije. Od tri glavne skupine opiodinih peptida, najviše dokaza o uključenosti u nociceptivne procese na spinalnoj razini dostupno je za enkefaline. Opioidni analgetici već dugo nalaze mjesto u kliničkoj primjeni, a novija istraživanja proučavaju njihov potencijal upotrebe u kroničnim bolestima, među kojima su i brojne upalne bolesti kao što su reumatoidni artritis ili osteoartritis. U ovom diplomskom radu mjerena je imunoreaktivnost enkefalina imunohistokemijskom metodom u uzorcima tkiva dorzalnog roga kralježnične moždine životinja kojima je prethodno uzrokovana upalna bol primjenom 5%-tne otopine formalina. Budući da se enkefalini smatraju endogenim tvarima s analgetskim učinkom koji učinak ostvaruju vezanjem za mi-opioidne receptore u dorzalnom rogu kralješnične moždine, očekivali smo da u stanjima upalne boli dolazi do njihove smanjene aktivacije. Suprotno očekivanom, ovim istraživanjem pokazali smo da nakon uzrokovanja upalne boli, dolazi do statistički značajnog porasta enkefalina u dorzalnom rogu kralješnične moždine. Premda je bolnost uzrokovana samo s jedne strane, povećanje imunoreaktivnosti mjereno je bilateralno. Ovi rezultati nas dovode do zaključka da usprkos povećanoj koncentraciji enkefalina, u stanjima hiperosjetljivosti dolazi do smanjenja broja ili osjetljivosti mi-, a vjerojatno i delta-opioidnih receptora preko kojih enkefalini ostvaruju svoje fiziološke učinke. Kako bi se skupili dodatni dokazi o navedenoj hipotezi, potrebna su daljna istraživanja koja će doprinijeti boljem razumjevanju uloge endogenog opioidnog sustava kod upalne boli te u konačnici rezultirati uporabom u kliničkoj praksi.

Abstract (english)

Inflammatory pain occurs as a result of inflammation or tissue mJury which causes the secretion of various inflammatory mediators that act directly by activating nociceptors or interfere with the signaling processes inside them. Frequent outbreak of primary neurons leads to numerous changes in CNS accompanied by phenomena such as sensitization, hyperalgesia and allodynia. Numerous studies have shown the important role of endogenous opioid system in the process of transmission and modulation of painful information. Out of three main groups of opioid peptides, most evidence of involvement in nociceptive processes in the spinal level is available for enkephalins. Opioid analgesics have long found a place in clinical practice. Recent research studies potential of their use in chronic diseases, among which are inflammatory diseases like rheumatoid arthritis or osteoarthritis. This thesis is based on measurment of enkephalin immunoreactivity in tissue samples of dorsal hom of the spinal cord of animals which had previously caused pain by using 5% formalin solution. Immunohistochemical methods were used. Since the endogenous enkephalins are considered as substances with analgesic effects that effect by binding to mu-opioid receptors in the dorsal horu of spinal cord, we expected their decreased activation in conditions of inflammatory pain. Contrary to expectations, this research has shown that, after causing inflammatory pain, there is a statistically significant increase in enkephalin concentration in the dorsaln hom of spinal cord. Although the pain was caused only on the one side of body, an increase in immunoreactivity was billateraly. These results lead us to the conclusion that, despite of the increased concentration of enkephalis, the states of hypersensitivity leads to reduced number or sensitivity of mu, and probably also delta-opioid receptors through which enkephalins effect their physiological effects. Further research is needed to gather more evidence on the above hypothesis in order to contribute to a better understanding of the role of the endogenous opiod system in inflammatory pain and ultimately result in its use in clinical practice.

• Keywords: bol; upalna bol; nociceptori; opioidi; imunohistokemija; enkefalini
• Keywords (english): pain; inflammatory pain; nociceptors; opioids; immunocytochemistry; enkephalins
• Language: croatian
• URN:NBN: urn:nbn:hr:163:000788
• Study programme: Title: Farmacija; Study programme type: sveučilišni; Study level: integrirani preddiplomski i diplomski; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-02-26 08:10:52