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Title: EXPRESS: Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models
Authors: Guo, Wei
Chu, Yu Xia
Imai, Satoshi  kyouindb  KAKEN_id
Yang, Jia Le
Zou, Shiping
Mohammad, Zaid
Wei, Feng
Dubner, Ronald
Ren, Ke
Author's alias: 今井, 哲司
Keywords: chronic constriction injury
mesenchymal stromal cells
Orofacial pain
spinal nerve injury
tendon ligation
trigeminal neuron
Issue Date: 1-Jul-2016
Publisher: SAGE Publications Inc.
Journal title: Molecular Pain
Volume: 12
Start page: 1
End page: 12
Abstract: 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 (PKCγ) 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 PKCγ 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.
Rights: © The Author(s) 2016. Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (
DOI(Published Version): 10.1177/1744806916658043
PubMed ID: 27329776
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