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Effect of the conditioned medium of mesenchymal stem cells on the expression levels of P2X4 and P2X7 purinergic receptors in the spinal cord of rats with neuropathic pain

Purinergic Signalling volume 17, pages 143–150 (2021)Cite this article

Abstract

Recent studies have shown that mesenchymal stem cells (MSCs) and their conditioned medium (CM) have potential therapeutic effects in animal models of neuropathic pain (NP). However, the mechanisms underlying these effects are not fully understood. Because of the leading involvement of purinergic receptors in the pathogenesis of NP, this study aimed to investigate the effect of MSCs-CM on the expression levels of P2X4 and P2X7 receptors in a rat model of NP induced by chronic constriction injury (CCI) of the sciatic nerve. CM was prepared from the rats’ bone marrow–derived MSCs culture. After that, NP rats were treated by intraperitoneal injection of CM, or Dulbecco’s modified Eagle’s medium (DMEM) 1 day before and 7 and 11 days after CCI surgery. The NP status was assessed in the treated animals using behavioral tests, including mechanical allodynia and thermal hyperalgesia, on days − 1, 3, 6, 9, 12, and 15 of the study. At the end of the study (Day 15), the animals were sacrificed, and the relative gene expression of P2X4 and P2X7 receptors were measured in the spinal cord using quantitative real-time PCR. The results demonstrated that in the CM-treated NP rats, mechanical allodynia and thermal hyperalgesia were significantly reduced compared with the DMEM-treated group. In addition, the expression levels of P2X4 and P2X7 receptors were noticeably prevented in the CM-treated group than the control group. These findings indicate that the antinociceptive effects of CM in the NP rats are partly mediated through preventing the upregulation of P2X4 and P2X7 receptors in the spinal cord.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgments

We thank Mrs. Falanji for her help on RT-PCR analysis.

Funding

This work was supported financially by the deputy of research and technology at Arak University of Medical Sciences.

Author information

Affiliations

  1. Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

    Mahsa Masoodifar, Saeed Hajihashemi & Saeed Pazhoohan

  2. Cellular and Molecular Research Center, Department of Physiology and Pharmacology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Samad Nazemi

  3. Leishmaniasis Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Mohammad-Shafi Mojadadi

Authors
  1. Mahsa Masoodifar
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  2. Saeed Hajihashemi
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  3. Saeed Pazhoohan
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  4. Samad Nazemi
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  5. Mohammad-Shafi Mojadadi
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Corresponding authors

Correspondence to Saeed Hajihashemi or Mohammad-Shafi Mojadadi.

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The authors declare that they have no conflict of interest.

Ethical approval

All experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Academy of Sciences (The National Academies Press, Washington, D.C, 8th edition) and the Basel Declaration. In addition, all methods were approved by the Research Ethics Committee of Arak University of Medical Sciences (IR.ARAKMU.1397.333).

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Masoodifar, M., Hajihashemi, S., Pazhoohan, S. et al. Effect of the conditioned medium of mesenchymal stem cells on the expression levels of P2X4 and P2X7 purinergic receptors in the spinal cord of rats with neuropathic pain. Purinergic Signalling 17, 143–150 (2021). https://doi.org/10.1007/s11302-020-09756-5

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  • DOI: https://doi.org/10.1007/s11302-020-09756-5

Keywords

  • Neuropathic pain
  • Mesenchymal stem cells
  • Conditioned medium
  • P2X4 receptor
  • P2X7 receptor
  • Hyperalgesia
  • Allodynia