PMID- 21630378
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20220330
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 29
IP  - 8
DP  - 2011 Aug
TI  - Bone marrow stromal cells produce long-term pain relief in rat models of 
      persistent pain.
PG  - 1294-303
LID - 10.1002/stem.667 [doi]
AB  - Chronic pain conditions are difficult to treat and are major health problems. 
      Bone marrow stromal cells (BMSCs) have generated considerable interest as a 
      candidate for cell-based therapy. BMSCs are readily accessible and are easy to 
      isolate and expand ex vivo. Clinical studies show that direct injection of BMSCs 
      does not produce unwanted side effects and is well tolerated and safe. Here, we 
      show that a single systemic (intravenous) or local injection (into the lesion 
      site) of rat primary BMSCs reversed pain hypersensitivity in rats after injury 
      and that the effect lasted until the conclusion of the study at 22 weeks. The 
      pain hypersensitivity was rekindled by naloxone hydrochloride, an opioid receptor 
      antagonist that acts peripherally and centrally, when tested at 1-5 weeks after 
      BMSC infusion. In contrast, naloxone methiodide, a peripherally acting opioid 
      receptor antagonist, only rekindled hyperalgesia in the first 3 weeks of BMSC 
      treatment. Focal downregulation of brainstem mu opioid receptors by RNA 
      interference (RNAi) reversed the effect of BMSCs, when RNAi was introduced at 5- 
      but not 1-week after BMSC transplantation. Thus, BMSCs produced long-term relief 
      of pain and this effect involved activation of peripheral and central opioid 
      receptors in distinct time domains. The findings prompt studies to elucidate the 
      cellular mechanisms of the BMSC-induced pain relieving effect and translate these 
      observations into clinical settings.
CI  - Copyright (c) 2011 AlphaMed Press.
FAU - Guo, Wei
AU  - Guo W
AD  - Department of Neural and Pain Sciences, Dental School, University of Maryland, 
      Baltimore, Maryland 21201-1586, USA.
FAU - Wang, Hu
AU  - Wang H
FAU - Zou, Shiping
AU  - Zou S
FAU - Gu, Ming
AU  - Gu M
FAU - Watanabe, Mineo
AU  - Watanabe M
FAU - Wei, Feng
AU  - Wei F
FAU - Dubner, Ronald
AU  - Dubner R
FAU - Huang, George T-J
AU  - Huang GT
FAU - Ren, Ke
AU  - Ren K
LA  - eng
GR  - NS059028/NS/NINDS NIH HHS/United States
GR  - R01 DE019156-05/DE/NIDCR NIH HHS/United States
GR  - R01 DE011964/DE/NIDCR NIH HHS/United States
GR  - DE018573/DE/NIDCR NIH HHS/United States
GR  - R01 NS059028/NS/NINDS NIH HHS/United States
GR  - R01 NS060735/NS/NINDS NIH HHS/United States
GR  - DE11964/DE/NIDCR NIH HHS/United States
GR  - R01 DE018573/DE/NIDCR NIH HHS/United States
GR  - NS060735/NS/NINDS NIH HHS/United States
GR  - R01 DE019156/DE/NIDCR NIH HHS/United States
GR  - DE019156/DE/NIDCR NIH HHS/United States
GR  - R01 DE019156-03/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Antigens, CD)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Receptors, Opioid, mu)
RN  - 36B82AMQ7N (Naloxone)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Bone Marrow Cells/metabolism
MH  - *Bone Marrow Transplantation
MH  - Cell Shape
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/metabolism
MH  - Myelencephalon/metabolism
MH  - Naloxone/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - *Pain Management
MH  - RNA Interference
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Opioid, mu/genetics/metabolism
MH  - Stromal Cells/metabolism/*transplantation
MH  - Tendon Injuries/therapy
PMC - PMC3277433
MID - NIHMS331028
COIS- Disclosure of Potential Conflicts of Interest The authors indicate no potential 
      conflicts of interest.
EDAT- 2011/06/02 06:00
MHDA- 2011/11/16 06:00
PMCR- 2012/02/10
CRDT- 2011/06/02 06:00
PHST- 2011/06/02 06:00 [entrez]
PHST- 2011/06/02 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
PHST- 2012/02/10 00:00 [pmc-release]
AID - 10.1002/stem.667 [doi]
PST - ppublish
SO  - Stem Cells. 2011 Aug;29(8):1294-303. doi: 10.1002/stem.667.