EXPRESS: Further observations on the behavioral and neural effects of bone marrow stromal cells in rodent pain models

• 今井, 哲司

  医学部附属病院薬剤部講師

• Chu, Yu Xia

• Imai, Satoshi

• Yang, Jia Le

• Zou, Shiping

• Mohammad, Zaid

• Wei, Feng

• Dubner, Ronald

• Ren, Ke

抄録

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.

収録刊行物

• Molecular Pain

  Molecular Pain 12 1-12, 2016-07-01

  SAGE Publications Inc.

キーワード

• chronic constriction injury
• mesenchymal stromal cells
• Orofacial pain
• spinal nerve injury
• tendon ligation
• trigeminal neuron

詳細情報

• CRID: 1050564285794472576
• NII論文ID: 120005973343
• ISSN: 17448069
• HANDLE: 2433/218317
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles