Document Detail

Morphine stimulates cell migration of oral epithelial cells by delta-opioid receptor activation.
MedLine Citation:
PMID:  22900034     Owner:  NLM     Status:  MEDLINE    
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.
Nada Charbaji; Monika Schäfer-Korting; Sarah Küchler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-10
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-08-17     Completed Date:  2013-03-22     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e42616     Citation Subset:  IM    
Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
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MeSH Terms
Cell Line
Cell Movement / drug effects*
Cell Proliferation / drug effects
Cell Survival / drug effects
Epithelial Cells / drug effects*,  metabolism*
Gene Expression
Mitogen-Activated Protein Kinases / metabolism
Morphine / pharmacology*
Mouth Mucosa / cytology*
Receptors, Opioid / agonists,  genetics,  metabolism
Receptors, Opioid, delta / agonists,  genetics,  metabolism*
Signal Transduction / drug effects
Wound Healing / drug effects,  genetics
Reg. No./Substance:
0/Receptors, Opioid; 0/Receptors, Opioid, delta; 57-27-2/Morphine; EC Protein Kinases

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