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Morphine stimulates cell migration of oral epithelial cells by delta-opioid receptor activation

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Item Type:Article
Title:Morphine stimulates cell migration of oral epithelial cells by delta-opioid receptor activation
Creators Name:Charbaji, N., Schäfer-Korting, M. and Küchler, S.
Abstract:Oral mucositis is one of the most common side effects of chemoradiation regimens and manifestation can be dose-limiting for the therapy, can impair the patient's nutritional condition and quality of life due to severe pain. The therapeutic options are limited; often only an alleviation of the symptoms such as pain reduction by using systemic opioids is possible. Stimulating opioid receptors on peripheral neurons and dermal tissue, potent analgesic effects are induced e.g. in skin grafted patients. Advantageous effects on the cell migration and, thus, on the wound healing process are described, too. In this study, we investigated whether opioid receptors are also expressed on oral epithelial cells and if morphine can modulate their cell migration behavior. The expression of the opioid receptors MOR, DOR and KOR on primary human oral epithelial cells was verified. Furthermore, a significantly accelerated cell migration was observed following incubation with morphine. The effect even slightly exceeded the cell migration stimulating effect of TGF-ß: After 14 h of morphine treatment about 86% of the wound area was closed, whereas TGF-ß application resulted in a closed wound area of 80%. With respect to morphine stimulated cell migration we demonstrate that DOR plays a key role and we show the involvement of the MAPK members Erk 1/2 and p38 using Western blot analysis. Further studies in more complex systems in vitro and in vivo are required. Nevertheless, these findings might open up a new therapeutic option for the treatment of oral mucositis.
Keywords:Cell Line, Cell Movement, Cell Proliferation, Cell Survival, Delta Opioid Receptors, Epithelial Cells, Gene Expression, Mitogen-Activated Protein Kinases, Morphine, Mouth Mucosa, Opioid Receptors, Signal Transduction, Wound Healing
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:7
Number:8
Page Range:e42616
Date:August 2012
Official Publication:https://doi.org/10.1371/journal.pone.0042616
PubMed:View item in PubMed

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