Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-15T13:26:07.776Z Has data issue: false hasContentIssue false
  • English
  • Français

Preemptive Stem Cells Ameliorate Neuropathic Pain in Rats: A Central Component of Preemptive Analgesia

Part of: Micrographia Collection

Published online by Cambridge University Press:  16 February 2021

Hassan I. Kotb ,
Abualauon M. Abedalmohsen ,
Ahmed F. Elgamal ,
Doaa M. Mokhtar Open the ORCID record for Doaa M. Mokhtar [Opens in a new window]  and
Rasha B. Abd-ellatief
Hassan I. Kotb
Affiliation:
Department of anesthesia, intensive care and pain management, Faculty of Medicine, Assiut University, Asyut, Egypt
Abualauon M. Abedalmohsen
Affiliation:
Department of anesthesia, intensive care and pain management, Faculty of Medicine, Assiut University, Asyut, Egypt
Ahmed F. Elgamal
Affiliation:
Department of anesthesia, intensive care and pain management, Faculty of Medicine, Assiut University, Asyut, Egypt
Doaa M. Mokhtar
Affiliation:
Department of anatomy and Histology, Faculty of Veterinary Medicine, Assiut University, Asyut, Egypt
Rasha B. Abd-ellatief*
Affiliation:
Department of pharmacology, Faculty of Medicine, Assiut University, Asyut, Egypt
*
*Author for correspondence: Rasha Abd-ellatief, E-mail: [email protected]
Get access

Abstract

The present study aims to investigate the efficacy of intravenously injected mesenchymal stem cells (MSCs) in treating neuropathic pain either before or after its induction by a chronic constriction injury (CCI) model. Rats were divided into four groups: control group, neuropathic group, and treated groups (pre and postinduction) with i.v. mononuclear cells (106 cell/mL). For these rats, experimental testing for both thermal and mechanical hyperalgesia was evaluated. The cerebral cortex of the rats was dissected, and immunohistochemical analysis using anti-proliferating cell nuclear antigen (PCNA), CD117, nestin, and glial fibrillary acidic protein was performed. Our results showed that a single injection of MSCs (either preemptive/or post-CCI) produced equipotent effects on allodynia, mechanical hyperalgesia, and thermal response. Immunohistochemical analysis showed that the stem cells have reached the cerebral cortex. The injected group with MSCs before CCI showing few stem cells expressed PCNA, CD117, and nestin in the cerebral cortex. The group injected with MSCs after CCI, showing numerous recently proliferated CD117-, nestin-, PCNA-positive stem cells in the cerebral cortex. In conclusion, our findings demonstrate that the most probable effect of i.v. stem cells is the central anti-inflammatory effect, which opens concerns about how stem cells circulating in systemic administration to reach the site of injury.

Keywords

CCIGFAPnestinneuropathic painstem cells
Type
Micrographia
Information
Microscopy and Microanalysis , Volume 27 , Issue 2 , April 2021 , pp. 450 - 456
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of the Microscopy Society of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bayati, V, Hashemitabar, M, Gazor, R, Nejatbakhsh, R & Bijannejad, D (2013). Expression of surface markers and myogenic potential of rat bone marrow- and adipose-derived stem cells: A comparative study. Anat Cell Biol 46(2), 113–121.CrossRefGoogle ScholarPubMed
Bennett, GJ & Xie, YK (1988). A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33(1), 87–107.CrossRefGoogle ScholarPubMed
Bernier, PJ, Bédard, A, Vinet, J, Lévesque, M & Parent, A (2002). Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci USA 99(17), 11464–11469.CrossRefGoogle ScholarPubMed
Chu, LW, Chen, JY, Yu, KL, Cheng, KI, Chen, IJ, Wu, PC & Wu, BN (2012). Neuroprotective and anti-inflammatory activities of atorvastatin in a rat chronic constriction injury model. Int J Immunopathol Pharmacol 25(1), 219–230.CrossRefGoogle Scholar
da Silva Meirelles, L, Fontes, AM, Covas, DT, & Caplan, AI (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20(5–6), 419–427.CrossRefGoogle Scholar
Dworkin, RH, Backonja, M, Rowbotham, MC, Allen, RR, Argoff, CR, Bennett, GJ & Hewitt, DJ (2003). Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Arch Neurol 60(11), 1524–1534.CrossRefGoogle ScholarPubMed
Edalatmanesh, MA, Bahrami, AR, Hosseini, E, Hosseini, M & Khatamsaz, S (2011). Neuroprotective effects of mesenchymal stem cell transplantation in animal model of cerebellar degeneration. Neurol Res 33(9), 913–920.CrossRefGoogle ScholarPubMed
Ellis, A & Bennett, DLH (2013). Neuroinflammation and the generation of neuropathic pain. Br J Anaesth 111(1), 26–37.CrossRefGoogle ScholarPubMed
Farghaly, HS, Abd-ellatief, RB, Moftah, MZ, Mostafa, MG, Khedr, EM & Kotb, HI (2014). The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model. Pain Physician 17(2), 187–195.CrossRefGoogle ScholarPubMed
Fortino, VR, Pelaez, D & Cheung, HS (2013). Concise review: Stem cell therapies for neuropathic pain. Stem Cells Transl Med 2(5), 394–399.CrossRefGoogle ScholarPubMed
Han, YH, Kim, KH, Abdi, S & Kim, TK (2019). Stem cell therapy in pain medicine. Korean J Pain 32(4), 245.CrossRefGoogle ScholarPubMed
Hellman, A, Maietta, T, Byraju, K, Park, YL, Shao, M, Liss, A & Nalwalk, J (2020). Low intensity focused ultrasound modulation of vincristine induced neuropathy. Neuroscience 430, 82–93.CrossRefGoogle ScholarPubMed
Huh, Y, Ji, RR & Chen, G (2017). Neuroinflammation, bone marrow stem cells, and chronic pain. Front Immunol 8, 1014.CrossRefGoogle ScholarPubMed
Klass, M, Gavrikov, V, Drury, D, Stewart, B, Hunter, S, Denson, DD & Csete, M (2007). Intravenous mononuclear marrow cells reverse neuropathic pain from experimental mononeuropathy. Anesth Analg 104(4), 944–948.CrossRefGoogle ScholarPubMed
Kriegstein, AR & Götz, M (2003). Radial glia diversity: A matter of cell fate. Glia 43(1), 37–43.CrossRefGoogle ScholarPubMed
Lendahl, U, Zimmerman, LB & McKay, RD (1990). CNS stem cells express a new class of intermediate filament protein. Cell 60(4), 585–595.CrossRefGoogle ScholarPubMed
Liu, L, Hua, Z, Shen, J, Yin, Y, Yang, J, Cheng, K & Cheng, J (2017). Comparative efficacy of multiple variables of mesenchymal stem cell transplantation for the treatment of neuropathic pain in rats. Mil Med 182(suppl_1), 175–184.CrossRefGoogle ScholarPubMed
Mehta, AK, Bhati, Y, Tripathi, CD & Sharma, KK (2014). Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats. Neurochem Res 39(8), 1433–1439.CrossRefGoogle ScholarPubMed
Müller, FJ, Snyder, EY & Loring, JF (2006). Gene therapy: Can neural stem cells deliver? Nat Rev Neurosci 7(1), 75–84.CrossRefGoogle ScholarPubMed
Ohira, K (2011). Injury-induced neurogenesis in the mammalian forebrain. Cell Mol Life Sci 68(10), 1645–1656.CrossRefGoogle ScholarPubMed
Ohira, K (2018). Regulation of adult neurogenesis in the cerebral cortex. J Neurol Neuromed 3, 59–64.CrossRefGoogle Scholar
Ossipov, MH (2011). Growth factors and neuropathic pain. Curr Pain Headache Rep 15(3), 185–192.CrossRefGoogle ScholarPubMed
Petrocchi, JA, de Almeida, DL, Paiva-Lima, P, Queiroz-Junior, C, Caliari, MV, Duarte, IDG & Romero, TRL (2019). Peripheral antinociception induced by ketamine is mediated by the endogenous opioid system. Eur J Pharmacol 865, 172808.CrossRefGoogle ScholarPubMed
Rankin, SL, Partlow, GD, McCurdy, RD, Giles, ED & Fisher, KR (2004). The use of proliferating cell nuclear antigen immunohistochemistry with a unique functional marker to detect postnatal neurogenesis in paraffin-embedded sections of the mature pig brain. Brain Res Protoc 13(2), 69–75.CrossRefGoogle ScholarPubMed
Sacerdote, P, Niada, S, Franchi, S, Arrigoni, E, Rossi, A, Yenagi, V & Brini, AT (2013). Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy. Stem Cells Dev 22(8), 1252–1263.CrossRefGoogle Scholar
Sangeetha, P, Maiti, SK, Divya Mohan, SS, Raguvaran, R, Malik, AR, Bindhuja, BV & Raguvanshi, PDS (2017). Mesenchymal stem cells derived from rat boné marrow (rBM MSC): Techniques for isolation, expansion and differentiation. J Stem Cell Res Ther 3(3), 00101.Google Scholar
Sommer, C, Leinders, M & Üçeyler, N (2018). Inflammation in the pathophysiology of neuropathic pain. Pain 159(3), 595–602.CrossRefGoogle ScholarPubMed
Vadivelu, S, Willsey, M, Curry, DJ & McDonald, JW (2013). Potential role of stem cells for neuropathic pain disorders. Neurosurg Focus 35(3), E11.CrossRefGoogle ScholarPubMed
Vickers, ER, Karsten, E, Flood, J & Lilischkis, R (2014). A preliminary report on stem cell therapy for neuropathic pain in humans. J Pain Res 7, 255.CrossRefGoogle ScholarPubMed
Yu, H, Fischer, G, Ebert, AD, Wu, HE, Bai, X & Hogan, QH (2015). Analgesia for neuropathic pain by dorsal root ganglion transplantation of genetically engineered mesenchymal stem cells: Initial results. Mol Pain 11, s12990–s13015.CrossRefGoogle ScholarPubMed
Zhang, EJ, Song, CH, Ko, YK & Lee, WH (2014). Intrathecal administration of mesenchymal stem cells reduces the reactive oxygen species and pain behavior in neuropathic rats. Korean J Pain 27(3), 239.CrossRefGoogle ScholarPubMed