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Identifier

000383017

Title

The role of regulator of G-protein signaling 20(RGS20) in inflammatory pain antinociception,opioid-induced analgesia and morphine tolerance

Alternative Title

Ο ρόλος της πρωτεϊνης RGS20στον φλεγμονωδη πόνο,την αναλγητική δράση των οπιοειδών και την αναλγητική ανοχή κατα τη χορήγηση μορφίνης

Author

Γάσπαρη, Σεβαστή

Thesis advisor

Ζαχαρίου, Βενετία

Reviewer

Καρδάσης, Δ
Πετράτος, Κ

Abstract

Chronic pain is probably the most prevalent human problem, contributing to individual morbidity and mortality and imposing high societal costs. Current management of chronic, non-cancer pain is far from optimal, with existing analgesics characterized by limited efficacy and a high adverse-effect burden. Opioid analgesics have been traditionally applied for the alleviation of severe pain conditions. Repeated opioid administration, however, may lead to a progressive decline in analgesic efficacy (tolerance) as well as the development of addiction. Investigation of the mechanisms involved in analgesic tolerance and dependence has provided a substantial insight into the neurobiology of these conditions. However, despite recent advances, the cellular and molecular alterations downstream of the receptor mediating opiate actions (the μ-opioid receptor (MOR)) are complex and still not well understood. Members of the regulators of G protein signaling (RGS) proteins have been associated with the regulation of several morphine actions, such as analgesia, reward and addiction. These proteins modulate signaling duration and desensitization of several G-protein coupled receptors (GPCRs), including the MOR. Previous studies from our laboratory have established the involvement of RGS9-2 and RGS4 in the mechanisms of opioid-derived analgesia and addiction. Here, by using Mus musculus model organism and well-established pain/opioid related behavioral assays we report the role of another RGS protein family member, RGS20, in inflammatory pain antinociception, opioid-induced analgesia and morphine tolerance. Specifically, we show that RGS20 seems to act as a negative regulator of opioid induced analgesia, but at the same time contributes to tolerance development in a PAG-mediated manner. Regarding addiction RGS20 does not seem to affect any dependence-related behavior. Moreover, RGS20 seems to act as a positive regulator of antinociception in chronic inflammatory pain conditions in a sex-dependent way. Together, the present data shed light on the actions of RGS20 protein providing novel information on its role in the cellular mechanisms underlying inflammatory pain conditions and morphine responses which will be important for the development of drug targets for the treatment of chronic pain.

Language

English

Subject

Analgesia

G-protein signaling

Inflammarory pain

Morphine

Opioids

RGS20

Tolerance

Αναλγησία

Οπιοεϊδή