Korean J Pain.  2014 Jul;27(3):239-245. 10.3344/kjp.2014.27.3.239.

Intrathecal Administration of Mesenchymal Stem Cells Reduces the Reactive Oxygen Species and Pain Behavior in Neuropathic Rats

• Zhang EJ
• Song CH
• Ko YK
• Lee WH

• KMID: 2278230
• DOI: http://doi.org/10.3344/kjp.2014.27.3.239

Abstract

BACKGROUND
Neuropathic pain induced by spinal or peripheral nerve injury is very resistant to common pain killers, nerve block, and other pain management approaches. Recently, several studies using stem cells suggested a new way to control the neuropatic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate whether intrathecal rat mesenchymal stem cells (rMSCs) were able to decrease pain behavior, as well as the relationship between rMSCs and reactive oxygen species (ROS).
METHODS
Neuropathic pain of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats (n = 10 in each group). Mechanical sensitivity was assessed using Von Frey filaments at 3, 7, 10, 12, 14, 17, and 24 days post-ligation. rMSCs (10 microl, 1 x 105) or phosphate buffer saline (PBS, 10 microl) was injected intrathecally at 7 days post-ligation. Dihydroethidium (DHE), an oxidative fluorescent dye, was used to detect ROS at 24 days post-ligation.
RESULTS
Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw after 3 days post-ligation. ROS expression was increased significantly (P < 0.05) in spinal dorsal horn of L5. Intrathecal rMSCs significantly (P < 0.01) alleviated the allodynia at 10 days after intrathecal injection (17 days post-ligation). Intrathecal rMSCs administration significantly (P < 0.05) reduced ROS expression in the spinal dorsal horn.
CONCLUSIONS
These results suggest that rMSCs may modulate neuropathic pain generation through ROS expression after spinal nerve ligation.

Keyword

mesenchymal stem cells; neuropathic pain; reactive oxygen species

MeSH Terms

Animals
Horns
Hyperalgesia
Injections, Spinal
Ligation
Mesenchymal Stromal Cells*
Nerve Block
Neuralgia
Pain Management
Peripheral Nerve Injuries
Rats*
Rats, Sprague-Dawley
Reactive Oxygen Species*
Spinal Nerves
Stem Cells
Reactive Oxygen Species

Figure

• 

  Fig. 1 Von Frey filament testing results. (A) Effect of spinal nerve ligation on the development of neuropathic pain. A significant decrease in the paw withdrawal threshold in the Von Frey filament test is induced 3 days after SNL. ***P < 0.001 vs. before surgery. (B) Effect of rMSCs on paw withdrawal reflex responses to Von Frey filament stimuli in rat pain models. rMSCs treatment on day 7 after SNL significantly increased the withdrawal threshold on days 10 and 17 after administration. **P < 0.01 vs. PBS group and #P < 0.05, ##P < 0.01 vs. Pain group. Values are expressed as the mean ± SEM (n = 10 in each group) Abbreviations: T, post-administration.

• 

  Fig. 2 DHE staining of the L5 spinal dorsal horn on day 24 following the spinal nerve ligation. (A) The L5 spinal dorsal horn segments (naive, pain, PBS, rMSCs groups) were stained with ROS-sensitive dye DHE (dihydroethidium). ROS (red) expression was decreased in the spinal cord of the rMSCs group (scale bar, 200 µm). (B) Fluorescent intensities of DHE signals were measured and compared with other groups. The intensities of DHE in the pain and PBS groups show a significant difference at *P < 0.05 compared with the naïve rats. The rMSCs group shows a statistical difference at #P < 0.05 compared with the pain or PBS groups. Values are expressed as the mean ± SEM.

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