Korean J Pain.  2020 Jan;33(1):23-29. 10.3344/kjp.2020.33.1.23.

The effect of human mesenchymal stem cell injection on pain behavior in chronic post-ischemia pain mice

• Yoo SH
• Lee SH
• Lee S
• Park JH
• Lee S
• Jin H
• Park HJ

• KMID: 2506639
• DOI: http://doi.org/10.3344/kjp.2020.33.1.23

Abstract

Background
Neuropathic pain (NP) is considered a clinically incurable condition despite various treatment options due to its diverse causes and complicated disease mechanisms. Since the early 2000s, multipotent human mesenchymal stem cells (hMSCs) have been used in the treatment of NP in animal models. However, the effects of hMSC injections have not been studied in chronic post-ischemia pain (CPIP) mice models. Here, we investigated whether intrathecal (IT) and intrapaw (IP) injections of hMSCs can reduce mechanical allodynia in CPIP model mice.
Methods
Seventeen CPIP C57/BL6 mice were selected and randomized into four groups: IT sham (n = 4), IT stem (n = 5), IP sham (n = 4), and IP stem (n = 4). Mice in the IT sham and IT stem groups received an injection of 5 μL saline and 2 × 10⁴ hMSCs, respectively, while mice in the IP sham and IP stem groups received an injection of 5 μL saline and 2 × 10 ⁵ hMSCs, respectively. Mechanical allodynia was assessed using von Frey filaments from pre-injection to 30 days post-injection. Glial fibrillary acidic protein (GFAP) expression in the spinal cord and dorsal root ganglia were also evaluated.
Results
IT and IP injections of hMSCs improved mechanical allodynia. GFAP expression was decreased on day 25 post-injection compared with the sham group. Injections of hMSCs improved allodynia and GFAP expression was decreased compared with the sham group.
Conclusions
These results suggested that hMSCs may be also another treatment modality in NP model by ischemia-reperfusion.

Keyword

Ganglia; Spinal; Glial Fibrillary Acidic Protein; Hyperalgesia; Mesenchymal Stromal Cells; Mice; Neuralgia; Reperfusion Injury; Spinal Cord; Stem Cells

Figure

• 

  Fig. 1 The anti-allodynic effects of human mesenchymal stem cells (hMSCs) on pain withdrawal threstholds in chronic post-ischemia pain mice model by von Frey filament testing. (A) Paw withdrawal mechanical thresholds were reduced after day 26 in left hindpaw of the intrapaw (IP) stem compared with pre-injection and sham-operated mice groups (*P < 0.05). Also the pain withdrawal threshold of the left hindpaw significantly increased at day 26–31 after stem cell injection in the intrathecal (IT) stem group compared with pre-injection and sham-operated mice groups († P < 0.05). (B) In the contra-lateral hindpaw, there no significant difference in pain withdrawal threshold between the groups.

• 

  Fig. 2 The expression of glial fibrillary acidic protein (GFAP) in the spinal cord and dorsal root ganglion (DRG). (A) In intrathecal (IT) stem and intrapaw (IP) stem groups, GFAP expression reduced in the spinal cord and DRG (200× magnification). (B) And there is a significant decrease in the staining density of GFAP at day 31 after injection of human mesenchymal stem cells compared with sham groups. ATF3: activating transcription factor 3. a P < 0.001 vs. IP sham, b P < 0.001 vs. IT sham.

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