2. Academic Validation
  3. Intrathecal injection of bone marrow stromal cells attenuates neuropathic pain via inhibition of P2X4R in spinal cord microglia

Intrathecal injection of bone marrow stromal cells attenuates neuropathic pain via inhibition of P2X4R in spinal cord microglia

  • J Neuroinflammation. 2019 Dec 17;16(1):271. doi: 10.1186/s12974-019-1631-0.
Yongbo Teng 1,  Yang Zhang 1 2,  Shouwei Yue 3,  Huanwen Chen 2,  Yujuan Qu 1,  Hui Wei 1,  Xiaofeng Jia 4 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan, China.
  • 2 Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • 3 Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan, China. [email protected].
  • 4 Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. [email protected].
  • 5 Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. [email protected].
  • 6 Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. [email protected].
  • 7 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. [email protected].
  • 8 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. [email protected].
PMID: 31847848 DOI: 10.1186/s12974-019-1631-0
Abstract

Background: Neuropathic pain is one of the most debilitating of all chronic pain syndromes. Intrathecal (i.t.) bone marrow stromal cell (BMSC) injections have a favorable safety profile; however, results have been inconsistent, and complete understanding of how BMSCs affect neuropathic pain remains elusive.

Methods: We evaluated the analgesic effect of BMSCs on neuropathic pain in a chronic compression of the dorsal root ganglion (CCD) model. We analyzed the effect of BMSCs on microglia reactivity and expression of purinergic receptor P2X4 (P2X4R). Furthermore, we assessed the effect of BMSCs on the expression of transient receptor potential vanilloid 4 (TRPV4), a key molecule in the pathogenesis of neuropathic pain, in dorsal root ganglion (DRG) neurons.

Results: I.t. BMSC transiently but significantly ameliorated neuropathic pain behavior (37.6% reduction for 2 days). We found no evidence of BMSC infiltration into the spinal cord parenchyma or DRGs, and we also demonstrated that intrathecal injection of BMSC-lysates provides similar relief. These findings suggest that the analgesic effects of i.t. BMSC were largely due to the release of BMSC-derived factors into the intrathecal space. Mechanistically, we found that while i.t. BMSCs did not change TRPV4 expression in DRG neurons, there was a significant reduction of P2X4R expression in the spinal cord microglia. BMSC-lysate also reduced P2X4R expression in activated microglia in vitro. Coadministration of additional pharmacological interventions targeting P2X4R confirmed that modulation of P2X4R might be a key mechanism for the analgesic effects of i.t. BMSC.

Conclusion: Altogether, our results suggest that i.t. BMSC is an effective and safe treatment of neuropathic pain and provides novel evidence that BMSC's analgesic effects are largely mediated by the release of BMSC-derived factors resulting in microglial P2X4R downregulation.

Keywords

Bone marrow stromal cells; Neuropathic pain; P2X4R; TRPV4.

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