The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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Intrathecal Administration of Mesenchymal Stem Cells Reduces the Reactive Oxygen Species and Pain Behavior in Neuropathic Rats

  • Zhang, En Ji (Department of Anesthesiology and Pain Medicine, Chungnam National University) ;
  • Song, Chang Hwa (Department of Microbiology, School of Medicine, Chungnam National University) ;
  • Ko, Young Kwon (Department of Anesthesiology and Pain Medicine, Chungnam National University) ;
  • Lee, Won Hyung (Department of Anesthesiology and Pain Medicine, Chungnam National University)
  • Received : 2014.03.12
  • Accepted : 2014.06.19
  • Published : 2014.07.01
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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 ($10{\mu}l$, $1{\times}10^5$) or phosphate buffer saline (PBS, $10{\mu}l$) 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.

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References

  1. Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175: 265-75. https://doi.org/10.1503/cmaj.060146
  2. Jaiswal RK, Jaiswal N, Bruder SP, Mbalaviele G, Marshak DR, Pittenger MF. Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 2000; 275: 9645-52. https://doi.org/10.1074/jbc.275.13.9645
  3. Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999; 181: 67-73. https://doi.org/10.1002/(SICI)1097-4652(199910)181:1<67::AID-JCP7>3.0.CO;2-C
  4. Lu L, Zhao C, Liu Y, Sun X, Duan C, Ji M, et al. Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease. Brain Res Brain Res Protoc 2005; 15: 46-51. https://doi.org/10.1016/j.brainresprot.2005.03.002
  5. Yang LY, Huang TH, Ma L. Bone marrow stromal cells express neural phenotypes in vitro and migrate in brain after transplantation in vivo. Biomed Environ Sci 2006; 19: 329-35.
  6. Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy 2005; 7: 36-45. https://doi.org/10.1080/14653240510018118
  7. Kim HK, Park SK, Zhou JL, Taglialatela G, Chung K, Coggeshall RE, et al. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 2004; 111: 116-24. https://doi.org/10.1016/j.pain.2004.06.008
  8. Wang ZQ, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E, et al. A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther 2004; 309: 869-78. https://doi.org/10.1124/jpet.103.064154
  9. Valle-Prieto A, Conget PA. Human mesenchymal stem cells efficiently manage oxidative stress. Stem Cells Dev 2010; 19: 1885-93. https://doi.org/10.1089/scd.2010.0093
  10. Tal M, Bennett GJ. Extra-territorial pain in rats with a peripheral mononeuropathy: mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve. Pain 1994; 57: 375-82. https://doi.org/10.1016/0304-3959(94)90013-2
  11. Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc 2009; 4: 102-6. https://doi.org/10.1038/nprot.2008.221
  12. Yang CC, Shih YH, Ko MH, Hsu SY, Cheng H, Fu YS. Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. PLoS One 2008; 3: e3336. https://doi.org/10.1371/journal.pone.0003336
  13. Papir-Kricheli D, Frey J, Laufer R, Gilon C, Chorev M, Selinger Z, et al. Behavioural effects of receptor-specific substance P agonists. Pain 1987; 31: 263-76. https://doi.org/10.1016/0304-3959(87)90041-8
  14. Harraz MM, Marden JJ, Zhou W, Zhang Y, Williams A, Sharov VS, et al. SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest 2008; 118: 659-70.
  15. Kumar S, Ruchi R, James SR, Chidiac EJ. Gene therapy for chronic neuropathic pain: how does it work and where do we stand today? Pain Med 2011; 12: 808-22. https://doi.org/10.1111/j.1526-4637.2011.01120.x
  16. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci 2005; 6: 521-32.
  17. Hill RG. Molecular basis for the perception of pain. Neuroscientist 2001; 7: 282-92. https://doi.org/10.1177/107385840100700405
  18. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007; 10: 1361-8. https://doi.org/10.1038/nn1992
  19. Reichling DB, Levine JD. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci 2009; 32: 611-8. https://doi.org/10.1016/j.tins.2009.07.007
  20. Kim D, You B, Jo EK, Han SK, Simon MI, Lee SJ. NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain. Proc Natl Acad Sci U S A 2010; 107: 14851-6. https://doi.org/10.1073/pnas.1009926107
  21. Siniscalco D, Giordano C, Rossi F, Maione S, de Novellis V. Role of neurotrophins in neuropathic pain. Curr Neuropharmacol 2011; 9: 523-9. https://doi.org/10.2174/157015911798376208
  22. Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 2004; 116: 639-48. https://doi.org/10.1016/S0092-8674(04)00208-9
  23. Siniscalco D, Giordano C, Galderisi U, Luongo L, Alessio N, Di Bernardo G, et al. Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice. Cell Mol Life Sci 2010; 67: 655-69. https://doi.org/10.1007/s00018-009-0202-4
  24. Savitz SI, Dinsmore JH, Wechsler LR, Rosenbaum DM, Caplan LR. Cell therapy for stroke. NeuroRx 2004; 1: 406-14. https://doi.org/10.1602/neurorx.1.4.406
  25. Levy YS, Bahat-Stroomza M, Barzilay R, Burshtein A, Bulvik S, Barhum Y, et al. Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson's disease. Cytotherapy 2008; 10: 340-52. https://doi.org/10.1080/14653240802021330
  26. Zurita M, Vaquero J. Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation. Neuroreport 2004; 15: 1105-8. https://doi.org/10.1097/00001756-200405190-00004
  27. Kim CH, Kim YW, Jang SH, Chang CH, Jung JH, Kim SH. Motor function recovery after adipose tissue derived mesenchymal stem cell therapy in rats with cerebral infarction. J Korean Neurosurg Soc 2006; 40: 267-72.
  28. Park ES, Gao X, Chung JM, Chung K. Levels of mitochondrial reactive oxygen species increase in rat neuropathic spinal dorsal horn neurons. Neurosci Lett 2006; 391: 108-11. https://doi.org/10.1016/j.neulet.2005.08.055

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