The effect of four weeks of physical activity in the enriched environment on inflammatory and anti-inflammatory factors in the dorsal horn of the spinal cord of mice with experimental autoimmune encephalomyelitis

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license

Authors

Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran.

Abstract

Aim: An excessive increase in the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) and a decrease in the levels of Tumor necrosis factor beta1 (TGF-β1) are associated with creating an inflammatory environment, resulting in increasing pain hypersensitivity in Different models of nerve pain. This study aimed to investigate the effect of four weeks of physical activity in an enriched environment on TNF-α, IL-1β, and TGF-β1 in the dorsal horn of the spinal cord in the chronic course of Experimental autoimmune encephalomyelitis (EAE).  Methods: Thirty female C57BL6 mice were divided into three groups: control, EAE, and enriched environment. After induction of EAE with MOG35-55, the environmental enrichment group lived in an enriched environment for four weeks. On day 30 post-induction (chronic period of the disease), pain sensitivity was assessed by tail immersion test in water, and then the animals were sacrificed and biopsied. TNF-α, IL-1β, and TGF-β1 protein levels were measured by immunohistochemistry. The data were analyzed by One-way analysis of variance at a significance level of 0.05. Results: The present study's findings showed that living in an enriched environment decreased the levels of TNF-α (p=0/00) and IL-1β (p=0/00) in the dorsal horn of the spinal cord and increased the level of TGF-β1 (p=0/00) protein compared to the EAE group. Also, physical activity in the enriched environment increased the delay time in extracting the tail from hot water in the chronic period of the disease (P = 0.00). Conclusions: Active lifestyle can reduce pain sensitivity in the animal model of MS disease (EAE) by reducing the levels of inflammatory factors TNF-α and IL-1β and increasing the levels of anti-inflammatory factor TGF-β1 in the dorsal horn of the spinal cord.

Keywords

Main Subjects

   

 

This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

References

  1. Rodrigues DH, Leles BP, Costa VV, Miranda AS, Cisalpino D, Gomes DA, et al. IL-1β Is Involved with the Generation of Pain in Experimental Autoimmune Encephalomyelitis. Mol Neurobiol. 2016;53(9):6540-7.
  2. Robinson RR, Dietz AK, Maroof AM, Asmis R, Forsthuber TG. The role of glial–neuronal metabolic cooperation in modulating progression of multiple sclerosis and neuropathic pain. Immunotherapy. 2019;11(2):129-47.
  3. Zhu J, Jankovic D, Oler AJ, Wei G, Sharma S, Hu G, et al. The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses. Immunity. 2012;37(4):660-73.
  4. Paintlia MK, Paintlia AS, Singh AK, Singh I. Synergistic activity of interleukin‐17 and tumor necrosis factor‐α enhances oxidative stress‐mediated oligodendrocyte apoptosis. Journal of neurochemistry. 2011;116(4):508-21.
  5. Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: A comprehensive review. J Autoimmun. 2015;64:13-25.
  6. Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, et al. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain. 2011;134(Pt 5):1293-314.
  7. Liu J, Gong N, Huang X, Reynolds AD, Mosley RL, Gendelman HE. Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration. J Immunol. 2009;182(6):3855-65.
  8. Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018;129(2):343-66.
  9. Barry A, Cronin O, Ryan AM, Sweeney B, Yap SM, O'Toole O, et al. Impact of Exercise on Innate Immunity in Multiple Sclerosis Progression and Symptomatology. Frontiers in Physiology. 2016;7(194).
  10. Xu JT, Xin WJ, Zang Y, Wu CY, Liu XG. The role of tumor necrosis factor-alpha in the neuropathic pain induced by Lumbar 5 ventral root transection in rat. Pain. 2006;123(3):306-21.
  11. Berta T, Park CK, Xu ZZ, Xie RG, Liu T, Lü N, et al. Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion. J Clin Invest. 2014;124(3):1173-86.
  12. Farajzadeh D, Karimi-Gharigh S, Dastmalchi S. Tumor necrosis factor-alpha and its inhibition strategies: review article. Tehran-Univ-Med-J. 2017;75(3):159-7]Iin persian[
  13. Fresegna D, Bullitta S, Musella A, Rizzo FR, De Vito F, Guadalupi L, et al. Re-Examining the Role of TNF in MS Pathogenesis and Therapy. Cells. 2020;9(10):2290.
  14. Rizzo F, Musella A, Vito F, Fresegna D, Bullitta S, Vanni V, et al. Tumor Necrosis Factor and Interleukin-1 β Modulate Synaptic Plasticity during Neuroinflammation. Neural Plasticity. 2018;2018:1-12.
  15. Chen NF, Huang SY, Chen WF, Chen CH, Lu CH, Chen CL, et al. TGF-β1 attenuates spinal neuroinflammation and the excitatory amino acid system in rats with neuropathic pain. J Pain. 2013;14(12):1671-85.
  16. Echeverry S, Shi XQ, Haw A, Liu H, Zhang ZW, Zhang J. Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects. Mol Pain. 2009;5:16.
  17. Boettger MK, Weber K, Grossmann D, Gajda M, Bauer R, Bär KJ, et al. Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation. Arthritis Rheum. 2010;62(5):1308-18.
  18. Zhang H, Li F, Li WW, Stary C, Clark JD, Xu S, et al. The inflammasome as a target for pain therapy. British Journal of Anaesthesia. 2016;117(6):693-707.
  19. Einstein O, Katz A, Ben-Hur T. Physical exercise therapy for autoimmune neuroinflammation: Application of knowledge from animal models to patient care. Autoimmunity Reviews. 2022;21(4):103033.
  20. Lozinski BM, Yong VW. Exercise and the brain in multiple sclerosis. Multiple Sclerosis Journal. 2020:1352458520969099.
  21. Saffar Kohneh Quchan AH, Kordi MR, Namdari H, Shabkhiz F. Voluntary wheel running stimulates the expression of Nrf-2 and interleukin-10 but suppresses interleukin-17 in experimental autoimmune encephalomyelitis. Neuroscience Letters. 2020;738:135382.
  22. Rahmati MR, Kordi MR, Ravasi AA. Effect of six weeks forced and voluntary training before EAE induction on the expression of some adhesive molecules affecting the blood-brain barrier permeability. Journal of Sport and Exercise Physiology. 2022;15(1):57-68.]in persian[
  23. Patel DI, White LJ. Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis. Applied Physiology, Nutrition, and Metabolism. 2013;38(2):194-9.
  24. Xie Y, Li Z, Wang Y, Xue X, Ma W, Zhang Y, et al. Effects of moderate- versus high- intensity swimming training on inflammatory and CD4(+) T cell subset profiles in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2019;328:60-7.
  25. Pryor WM, Freeman KG, Larson RD, Edwards GL, White LJ. Chronic exercise confers neuroprotection in experimental autoimmune encephalomyelitis. J Neurosci Res. 2015;93(5):697-706.
  26. Mifflin KA, Yousuf MS, Thorburn KC, Huang J, Pérez-Muñoz ME, Tenorio G, et al. Voluntary wheel running reveals sex-specific nociceptive factors in murine experimental autoimmune encephalomyelitis. Pain. 2019;160(4):870-81.
  27. Silva BA, Ferrari CC. Environmental enrichment as a promising strategy for aiding multiple sclerosis treatment. Neural Regen Res. 2020;15(9):1660-1.
  28. Shahidi SH, Kordi MR, Rajabi H, Malm C, Shah F, Quchan ASK. Exercise modulates the levels of growth inhibitor genes before and after multiple sclerosis. Journal of Neuroimmunology. 2020;341:577172.
  29. Fournier AP, Baudron E, Wagnon I, Aubert P, Vivien D, Neunlist M, et al. Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis. Mult Scler J Exp Transl Clin. 2020;6(4):2055217320959806.
  30. Li Z, Wang Y, Zhao J, Zhang H. Dieckol attenuates the nociception and inflammatory responses in different nociceptive and inflammatory induced mice model. Saudi Journal of Biological Sciences. 2021;28(9):4891-9.
  31. Rodrigues DH, Leles BP, Costa VV, Miranda AS, Cisalpino D, Gomes DA, et al. IL-1β Is Involved with the Generation of Pain in Experimental Autoimmune Encephalomyelitis. Mol Neurobiol. 2016;53(9):6540-7.
  32. Begum F, Zhu W, Cortes C, MacNeil B, Namaka M. Elevation of tumor necrosis factor α in dorsal root ganglia and spinal cord is associated with neuroimmune modulation of pain in an animal model of multiple sclerosis. J Neuroimmune Pharmacol. 2013;8(3):677-90.
  33. Ji R-R, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018;129(2):343-66.
  34. Leitzelar BN, Koltyn KF. Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research. Sports Med Open. 2021;7(1):21-.
  35. Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport. 1996;7(18):2897-901.
  36. Zanella JM, Burright EN, Hildebrand K, Hobot C, Cox M, Christoferson L, et al. Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model. Spine (Phila Pa 1976). 2008;33(3):227-34.
  37. Zhang L, Berta T, Xu ZZ, Liu T, Park JY, Ji RR. TNF-α contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2. Pain. 2011;152(2):419-27.
  38. Dobolyi A, Vincze C, Pál G, Lovas G. The neuroprotective functions of transforming growth factor beta proteins. Int J Mol Sci. 2012;13(7):8219-58.
  39. Chen NF, Chen WF, Sung CS, Lu CH, Chen CL, Hung HC, et al. Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats. J Headache Pain. 2016;17(1):72.
  40. Wang J, Xiang H, Lu Y, Wu T. Role and clinical significance of TGF‑β1 and TGF‑βR1 in malignant tumors (Review). Int J Mol Med. 2021;47(4):55.
Journal of Applied Health Studies in Sport Physiology
Volume 9, Issue 2
August 2022
Pages 138-148

Files

History

  • Receive Date: 23 June 2022
  • Revise Date: 29 October 2022
  • Accept Date: 05 November 2022

Share

How to cite

Statistics