Mesenchymal Stem Cells Reversed Morphine Tolerance and Opioid-induced Hyperalgesia.

Abstract

More than 240 million opioid prescriptions are dispensed annually to treat pain in the US. The use of opioids is commonly associated with opioid tolerance (OT) and opioid-induced hyperalgesia (OIH), which limit efficacy and compromise safety. The dearth of effective way to prevent or treat OT and OIH is a major medical challenge. We hypothesized that mesenchymal stem cells (MSCs) attenuate OT and OIH in rats and mice based on the understanding that MSCs possess remarkable anti-inflammatory properties and that both OT and chronic pain are associated with neuroinflammation in the spinal cord. We found that the development of OT and OIH was effectively prevented by either intravenous or intrathecal MSC transplantation (MSC-TP), which was performed before morphine treatment. Remarkably, established OT and OIH were significantly reversed by either intravenous or intrathecal MSCs when cells were transplanted after repeated morphine injections. The animals did not show any abnormality in vital organs or functions. Immunohistochemistry revealed that the treatments significantly reduced activation level of microglia and astrocytes in the spinal cord. We have thus demonstrated that MSC-TP promises to be a potentially safe and effective way to prevent and reverse two of the major problems of opioid therapy.

• Authors: Zhen Hua, LiPing Liu, Jun Shen, Kathleen Cheng, Aijun Liu, Jing Yang, Lina Wang, Tingyu Qu, HongNa Yang, Yan Li, Haiyan Wu, John Narouze, Yan Yin, Jianguo Cheng
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 32096 (08 24 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27554341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Aif1 protein, rat
• Calcium-Binding Proteins
• GFAP protein, rat
• Glial Fibrillary Acidic Protein
• Microfilament Proteins
• Morphine

Topics

• Animals
• Astrocytes (cytology)
• Calcium-Binding Proteins (metabolism)
• Cell Differentiation
• Drug Tolerance (physiology)
• Glial Fibrillary Acidic Protein (metabolism)
• Hyperalgesia (chemically induced, therapy)
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (cytology)
• Mice, Inbred C57BL
• Microfilament Proteins (metabolism)
• Microglia (cytology, drug effects)
• Morphine (pharmacology)
• Rats, Sprague-Dawley
• Spinal Cord (cytology, drug effects)