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Identifier

000388997

Title

Effect and mechanism of action of neurosteroids in inflammation -induced analgesia

Alternative Title

Ο ρόλος και ο μηχανισμός δράσης των νευροστεροειδών στην επαγώμενη απο φλεγμονή αναλγησία

Author

Πουλάκη, Σμαράγδα

Thesis advisor

Βενυχάκη, Μαρία

Reviewer

Θερμού, Κυριακη
Χαραλαμπόπουλος, Ιωάννης

Abstract

Pain is an unpleasant perception often caused by intense or damaging stimuli. Many types of pain have been described according to its different components, such as duration, location, and type of system that influences. In this study, we focused on inflammatory pain that occurs after tissue injury or infection, and is interwoven with immune system response. This situation causes discomfortness, stress and fear to the individual, but pain is also protective by preventing the individual to further use the injured member. Neurosteroids, like DHEA and Allopregnanolone have been demonstrated to exert positive effects in pain and hyperalgesia, as has been shown in pain models like caraggeenan-induced inflammation. A new synthetic analogue of DHEA has been recently developed, which conserves the immunomodulatory effects of DHEA, but lacks the endocrine properties of it (BNN27). Thus, the aim of our study was to examine the effect of BNN27 on inflammatory pain using the mouse model of inflammation and hyperalgesia induced by Complete’s Freund’s Adjuvant (CFA) in hind paw. Specifically, we focused on the contribution of BNN27 in basal and inflammatory pain, and edema and the mechanism BNN27 likely mediates its effects, through. Our results demonstrated that BNN27 has positive effect on basal and inflammatory pain, as it increased pain thresholds in treated mice, but it did not influence edema. BNN27 increased protein levels of TNF-a, IL-6, and NGF at 6 hours following the induction of inflammation, while it decreased TNF-aat 24 hours following inflammation. IL-6 and NGF were unchanged at 24 hours, while IL-10 was elevated in BNN27-treated mice at all time points examined. In DRGs, NGF was decreased at 6 and 24 hours after CFA injection. The analgesic affect of BNN27 seems to be mediated by μ-opioid receptor (MOR), as its mRNA expression levels were elevated in inflamed tissue and DRGs. M-opioid receptor ligand, β-endorphin and its precursor POMC were also elevated at 6 hours, while the mRNA of PENK, the precursor of enkephalins, was elevated at 24 hours. Our data indicate a potential role of BNN27 on inflammatory pain. Most studies with this compound so far were focused on its beneficial effect in neuroprotection. Here we show its positive contribution in another system, that of 6 pain and inflammation. Further studies are in progress to clarify its role and the mechanism in these conditions.

Language

English

Subject

Cytokines

Inflammation

Neurosteroids

Pain

Κυτοκίνες

Νευροστεροειδή

Νευροτροφίνες

Πόνος

Φλεγμονή