PMID- 27329776
OWN - NLM
STAT- MEDLINE
DCOM- 20161226
LR  - 20181202
IS  - 1744-8069 (Electronic)
IS  - 1744-8069 (Linking)
VI  - 12
DP  - 2016
TI  - Further observations on the behavioral and neural effects of bone marrow stromal 
      cells in rodent pain models.
LID - 10.1177/1744806916658043 [doi]
LID - 1744806916658043
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) have shown potential to treat 
      chronic pain, although much still needs to be learned about their efficacy and 
      mechanisms of action under different pain conditions. Here, we provide further 
      convergent evidence on the effects of BMSCs in rodent pain models. RESULTS: In an 
      orofacial pain model involving injury of a tendon of the masseter muscle, BMSCs 
      attenuated behavioral pain conditions assessed by von Frey filaments and a 
      conditioned place avoidance test in female Sprague-Dawley rats. The 
      antihyperalgesia of BMSCs in females lasted for <8 weeks, which is shorter than 
      that seen in males. To relate preclinical findings to human clinical conditions, 
      we used human BMSCs. Human BMSCs (1.5 M cells, i.v.) attenuated mechanical and 
      thermal hyperalgesia induced by spinal nerve ligation and suppressed spinal nerve 
      ligation-induced aversive behavior, and the effect persisted through the 8-week 
      observation period. In a trigeminal slice preparation, BMSC-treated and 
      nerve-injured C57B/L mice showed reduced amplitude and frequency of spontaneous 
      excitatory postsynaptic currents, as well as excitatory synaptic currents evoked 
      by electrical stimulation of the trigeminal nerve root, suggesting inhibition of 
      trigeminal neuronal hyperexcitability and primary afferent input by BMSCs. 
      Finally, we observed that GluN2A (N-methyl-D-aspartate receptor subunit 2A) 
      tyrosine phosphorylation and protein kinase Cgamma (PKCg) immunoreactivity in 
      rostral ventromedial medulla was suppressed at 8 weeks after BMSC in 
      tendon-injured rats. CONCLUSIONS: Collectively, the present work adds convergent 
      evidence supporting the use of BMSCs in pain control. As PKCg activity related to 
      N-methyl-D-aspartate receptor activation is critical in opioid tolerance, these 
      results help to understand the mechanisms of BMSC-produced long-term 
      antihyperalgesia, which requires opioid receptors in rostral ventromedial medulla 
      and apparently lacks the development of tolerance.
FAU - Guo, Wei
AU  - Guo W
AD  - University of Maryland School of Denstistry.
FAU - Chu, Yu-Xia
AU  - Chu YX
AD  - University of Maryland School of DenstistryUniversity of Maryland School of 
      DentistryUniversity of Maryland School of DentristryUniversity of Maryland School 
      of DentistryUniversity of Maryland School of Dentistry.
FAU - Imai, Satoshi
AU  - Imai S
AD  - University of Maryland School of DenstistryUniversity of Maryland School of 
      DentistryUniversity of Maryland School of DentristryUniversity of Maryland School 
      of DentistryUniversity of Maryland School of Dentistry.
FAU - Yang, Jia-Le
AU  - Yang JL
AD  - University of Maryland School of Dentistry.
FAU - Zou, Shiping
AU  - Zou S
AD  - University of Maryland School of Dentristry.
FAU - Mohammad, Zaid
AU  - Mohammad Z
AD  - University of Maryland School of Dentistry.
FAU - Wei, Feng
AU  - Wei F
AD  - University of Maryland School of DenstistryUniversity of Maryland School of 
      DentistryUniversity of Maryland School of DentristryUniversity of Maryland School 
      of DentistryUniversity of Maryland School of Dentistry.
FAU - Dubner, Ronald
AU  - Dubner R
AD  - University of Maryland School of Dentistry.
FAU - Ren, Ke
AU  - Ren K
AD  - University of Maryland School of DenstistryUniversity of Maryland School of 
      DentistryUniversity of Maryland School of DentristryUniversity of Maryland School 
      of DentistryUniversity of Maryland School of Dentistry kren@umaryland.edu.
LA  - eng
GR  - R01 DE025137/DE/NIDCR NIH HHS/United States
GR  - DE021804/DE/NIDCR NIH HHS/United States
GR  - DE025137/DE/NIDCR NIH HHS/United States
GR  - NS019296/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160621
PL  - United States
TA  - Mol Pain
JT  - Molecular pain
JID - 101242662
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 36B82AMQ7N (Naloxone)
RN  - EC 2.7.1.- (protein kinase C gamma)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - *Behavior, Animal
MH  - Brain/*pathology
MH  - Disease Models, Animal
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Female
MH  - Humans
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Mice, Inbred C57BL
MH  - Naloxone/pharmacology
MH  - Neuralgia/metabolism/pathology/*therapy
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Synapses/drug effects/pathology
MH  - Tendons/drug effects/pathology
MH  - Trigeminal Nerve/drug effects/pathology
PMC - PMC4956005
EDAT- 2016/06/23 06:00
MHDA- 2016/12/27 06:00
PMCR- 2016/06/21
CRDT- 2016/06/23 06:00
PHST- 2016/06/23 06:00 [entrez]
PHST- 2016/06/23 06:00 [pubmed]
PHST- 2016/12/27 06:00 [medline]
PHST- 2016/06/21 00:00 [pmc-release]
AID - 12/0/1744806916658043 [pii]
AID - 10.1177_1744806916658043 [pii]
AID - 10.1177/1744806916658043 [doi]
PST - epublish
SO  - Mol Pain. 2016 Jun 21;12:1744806916658043. doi: 10.1177/1744806916658043. Print 
      2016.