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Anesth Analg 2008; 107:686-692
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31817e6719
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ANALGESIA

Prolonged Use of High-Dose Morphine Impairs Angiogenesis and Mobilization of Endothelial Progenitor Cells in Mice

Chen-Fuh Lam, MD, PhD*, Pei-Jung Chang, MD*, Yu-Sheng Huang, MD*, Yen-Hui Sung, MD*, Chien-Chi Huang, BS*, Ming-Wei Lin, MS*{dagger}, Yen-Chin Liu, MD, MS*, and Yu-Chuan Tsai, MD*

From the *Department of Anesthesiology; and {dagger}Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.

Address correspondence and reprint requests to Yu-Chuan Tsai, MD, Department of Anesthesiology, National Cheng Kung University, Medical College and Hospital, Tainan City, Taiwan. Address e-mail to yctsai{at}mail.ncku.edu.tw.

Abstract

BACKGROUND: Morphine is one of the most commonly prescribed analgesics for treating wound pain. Using a mouse model of excisional wound injury, we determined the effects of high-dose morphine on angiogenesis and mobilization of endothelial progenitor cells.

METHODS: An excisional wound was created on mice treated with placebo or morphine (20 mg/kg, i.p. injection for 14 days). Wound healing was compared by measuring the final-to-initial wound area ratio. Generation of superoxide anions in the wound was determined by luminol-enhanced chemiluminescence. Circulating mononuclear cells were isolated and measured for endothelial progenitor cell (defined as CD34+/CD133+ cell) counts. In vivo and in vitro measurements of angiogenesis after morphine treatment were performed using the Matrigel assay.

RESULTS: Mice treated with morphine had reduced wound closure and higher wound superoxide ions concentrations than control mice. Morphine reduced the number of postwound circulating endothelial progenitor cells. Matrigel assay showed impaired angiogenesis in animals and reduced capillary tube formation in cultured endothelial cells treated with morphine.

CONCLUSION: High-dose morphine impaired angiogenesis, increased systemic oxidative stress, and impaired mobilization of endothelial progenitor cells. This study emphasizes the potential detrimental effect of high-dose morphine on angiogenesis after systemic administration.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.