The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities

  • I Nyoman, Semita (Medical Science, Faculty of Medicine, Airlangga University) ;
  • Dwikora Novembri, Utomo (Department of Orthopaedic, Faculty of Medicine, Airlangga University) ;
  • Heri, Suroto (Department of Orthopaedic, Faculty of Medicine, Airlangga University) ;
  • I Ketut, Sudiana (Department of Anatomic Pathology, Faculty of Medicine, Airlangga University) ;
  • Parama, Gandi (Departement of Cardiology, Faculty of Medicine, Airlangga University)
  • Received : 2022.08.12
  • Accepted : 2022.11.13
  • Published : 2023.01.01
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Abstract

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Keywords

Acknowledgement

The authors would like to thank Prof. Dr. dr. Ismail Hadisoebroto Dilogo, Sp.OT(K) for his support and advice during the research.

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