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Published in: Inflammation 3/2014

01-06-2014

Transcutaneous Electrical Nerve Stimulation (TENS) Accelerates Cutaneous Wound Healing and Inhibits Pro-inflammatory Cytokines

Authors: Seren Gülşen Gürgen, Oya Sayın, Ferihan Çetin, Ayşe Tuç Yücel

Published in: Inflammation | Issue 3/2014

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ABSTRACT

The purpose of this study was to evaluate transcutaneous electrical nerve stimulation (TENS) and other common treatment methods used in the process of wound healing in terms of the expression levels of pro-inflammatory cytokines. In the study, 24 female and 24 male adult Wistar–Albino rats were divided into five groups: (1) the non-wounded group having no incision wounds, (2) the control group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the physiological saline (PS) group and (5) the povidone iodine (PI) group. In the skin sections, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed with enzyme-linked immunosorbent assay and immunohistochemical methods. In the non-wounded group, the expression of IL-1β, IL-6, and TNF-α signaling molecules was weaker in the whole tissue; however, in the control group, significant inflammatory response occurred, and strong cytokine expression was observed in the dermis, granulation tissue, hair follicles, and sebaceous glands (P < 0.05). In the TENS group, the decrease in TNF-α, IL-1β, and IL-6 immunoreaction in the skin was significant compared to the other forms of treatment (P < 0.05). Distinctive decreases of pro-inflammatory cytokines observed in the dermis in the TENS group suggest that TENS shortened the healing process by inhibating the inflammation phase.
Literature
1.
go back to reference Singer, A.J., and R.A.F. Clark. 1999. Cutaneous wound healing. The New England Journal of Medicine 341: 738–746.PubMedCrossRef Singer, A.J., and R.A.F. Clark. 1999. Cutaneous wound healing. The New England Journal of Medicine 341: 738–746.PubMedCrossRef
2.
go back to reference Schaffer, M., and A. Barbul. 1998. Lymphocyte function in wound healing and following injury. The British Journal of Surgery 85: 444–460.PubMedCrossRef Schaffer, M., and A. Barbul. 1998. Lymphocyte function in wound healing and following injury. The British Journal of Surgery 85: 444–460.PubMedCrossRef
3.
go back to reference Heo, S.C., E.S. Jeon, I.H. Lee, H.S. Kim, M.B. Kim, and J.H. Kim. 2011. Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. The Journal of Investigative Dermatology 131: 1559–1567.PubMedCrossRef Heo, S.C., E.S. Jeon, I.H. Lee, H.S. Kim, M.B. Kim, and J.H. Kim. 2011. Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. The Journal of Investigative Dermatology 131: 1559–1567.PubMedCrossRef
4.
go back to reference Efron, P., and L. Moldawer. 2004. Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. Journal of Burn Care and Research 25: 149.CrossRef Efron, P., and L. Moldawer. 2004. Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. Journal of Burn Care and Research 25: 149.CrossRef
5.
go back to reference Werner, S., and R. Grose. 2003. Regulation of wound healing by growth factors and cytokines. Physiological Reviews 83: 835–870.PubMed Werner, S., and R. Grose. 2003. Regulation of wound healing by growth factors and cytokines. Physiological Reviews 83: 835–870.PubMed
6.
go back to reference Alvarez, O.M., P.M. Mertz, R.V. Smerbeck, and W.H. Eaglstein. 1983. The healing of superficial skin wounds is stimulated by external electrical current. The Journal of Investigative Dermatology 81: 144–148.PubMedCrossRef Alvarez, O.M., P.M. Mertz, R.V. Smerbeck, and W.H. Eaglstein. 1983. The healing of superficial skin wounds is stimulated by external electrical current. The Journal of Investigative Dermatology 81: 144–148.PubMedCrossRef
7.
go back to reference Brown, M., M.K. McDonnell, and D.N. Menton. 1989. Polarity effects on wound healing using electric stimulation in rabbits. Archives of Physical Medicine and Rehabilitation 70: 624–627.PubMed Brown, M., M.K. McDonnell, and D.N. Menton. 1989. Polarity effects on wound healing using electric stimulation in rabbits. Archives of Physical Medicine and Rehabilitation 70: 624–627.PubMed
8.
go back to reference Stromberg, B.V. 1988. Effects of electrical currents on wound contraction. Annals of Plastic Surgery 21: 121–123.PubMedCrossRef Stromberg, B.V. 1988. Effects of electrical currents on wound contraction. Annals of Plastic Surgery 21: 121–123.PubMedCrossRef
9.
go back to reference Kjartansson, J., T. Lundeberg, U.E. Samuelson, and C.J. Dalsgaard. 1988. Transcutaneous electrical nerve stimulation (TENS) increases survival of ischaemic musculocutaneous flaps. Acta Physiologica Scandinavica 13: 95–99.CrossRef Kjartansson, J., T. Lundeberg, U.E. Samuelson, and C.J. Dalsgaard. 1988. Transcutaneous electrical nerve stimulation (TENS) increases survival of ischaemic musculocutaneous flaps. Acta Physiologica Scandinavica 13: 95–99.CrossRef
10.
go back to reference Koca Kutlu, A., D. Ceçen, S.G. Gürgen, O. Sayın, and F. Cetin. A comparison study of growth factor expression following treatment with transcutaneous electrical nerve stimulation, saline solution, povidone–ıodine, and lavender oil in wounds healing. Evidence-based complementary and alternative medicine: eCAM 2013; 361832. doi:10.1155/2013/361832. Koca Kutlu, A., D. Ceçen, S.G. Gürgen, O. Sayın, and F. Cetin. A comparison study of growth factor expression following treatment with transcutaneous electrical nerve stimulation, saline solution, povidone–ıodine, and lavender oil in wounds healing. Evidence-based complementary and alternative medicine: eCAM 2013; 361832. doi:10.​1155/​2013/​361832.
11.
go back to reference Morgan, D.A. 1999. Wound management products in the Drug Tariff. The Pharmaceutical Journal 263: 820–825. Morgan, D.A. 1999. Wound management products in the Drug Tariff. The Pharmaceutical Journal 263: 820–825.
12.
go back to reference Jacobson, S. 2004. The wrong solution. Emergency Medicine 36: 13. Jacobson, S. 2004. The wrong solution. Emergency Medicine 36: 13.
13.
go back to reference Huxtable, K. 1993. Ritual cleansing. Nursing New Zealand 1: 14–16.PubMed Huxtable, K. 1993. Ritual cleansing. Nursing New Zealand 1: 14–16.PubMed
14.
go back to reference Kramer, S.A. 1999. Effect of povidone–iodine on wound healing: a review. Journal of Vascular Nursing 17: 17–23.PubMedCrossRef Kramer, S.A. 1999. Effect of povidone–iodine on wound healing: a review. Journal of Vascular Nursing 17: 17–23.PubMedCrossRef
15.
go back to reference Vermeulen, H., S.J. Westerbos, and D.T. Ubbink. 2010. Benefit and harm of iodine in wound care: a systematic review. The Journal of Hospital Infection 76: 191–199.PubMedCrossRef Vermeulen, H., S.J. Westerbos, and D.T. Ubbink. 2010. Benefit and harm of iodine in wound care: a systematic review. The Journal of Hospital Infection 76: 191–199.PubMedCrossRef
16.
go back to reference Goldenheim, P.D. 1993. An appraisal of povidone iodin and wound healing. Post Graduate Medical Journal 69: 97–105. Goldenheim, P.D. 1993. An appraisal of povidone iodin and wound healing. Post Graduate Medical Journal 69: 97–105.
17.
go back to reference Lineaweaver, W., R. Howard, D. Soucy, S. McMorris, J. Freeman, C. Crain, J. Robertson, and T. Rumley. 1985. Topical antimicrobial toxicity. Archives of Surgery 120: 267–270.PubMedCrossRef Lineaweaver, W., R. Howard, D. Soucy, S. McMorris, J. Freeman, C. Crain, J. Robertson, and T. Rumley. 1985. Topical antimicrobial toxicity. Archives of Surgery 120: 267–270.PubMedCrossRef
18.
go back to reference Burks, R.I. 1998. Povidone–iodine solution in wound treatment. Physical Therapy 78: 212–218.PubMed Burks, R.I. 1998. Povidone–iodine solution in wound treatment. Physical Therapy 78: 212–218.PubMed
19.
go back to reference Kondo, T., and T. Ohshima. 1996. The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. International Journal of Legal Medicine 108: 231–236.PubMedCrossRef Kondo, T., and T. Ohshima. 1996. The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. International Journal of Legal Medicine 108: 231–236.PubMedCrossRef
20.
go back to reference Lusby, P.E., A.L. Coombes, and J.M. Wilkinson. 2006. A comparison of wound healing following treatment with Lavandula x allardii honey or essential oil. Phytotherapy Research 20: 755–757.PubMedCrossRef Lusby, P.E., A.L. Coombes, and J.M. Wilkinson. 2006. A comparison of wound healing following treatment with Lavandula x allardii honey or essential oil. Phytotherapy Research 20: 755–757.PubMedCrossRef
21.
go back to reference Gürgen, S.G., D. Erdoğan, C. Elmas, G.T. Kaplanoğlu, and C. Ozer. 2013. Chemoprotective effect of ascorbic acid, α-tocopherol, and selenium on cyclophosphamide-induced toxicity in the rat ovarium. Nutrition 16: 1–8. Gürgen, S.G., D. Erdoğan, C. Elmas, G.T. Kaplanoğlu, and C. Ozer. 2013. Chemoprotective effect of ascorbic acid, α-tocopherol, and selenium on cyclophosphamide-induced toxicity in the rat ovarium. Nutrition 16: 1–8.
22.
go back to reference Cheing, G.L., and C.W. Hui-Chan. 1999. Transcutaneous electrical nevre stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain. Archives of Physical Medicine and Rehabilitation 80: 305–312.PubMedCrossRef Cheing, G.L., and C.W. Hui-Chan. 1999. Transcutaneous electrical nevre stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain. Archives of Physical Medicine and Rehabilitation 80: 305–312.PubMedCrossRef
23.
go back to reference Scudds, R.J., A. Helewa, and R.A. Scudds. 1995. The effects of transcutaneous electrical nerve stimulation on skin temperature in assintomatic subjects. Physical Therapy 75: 622–628. Scudds, R.J., A. Helewa, and R.A. Scudds. 1995. The effects of transcutaneous electrical nerve stimulation on skin temperature in assintomatic subjects. Physical Therapy 75: 622–628.
24.
go back to reference Kaada, B., E. Olsen, and O. Eielsen. 1984. In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation: III. Increase in plasma VIP in normal subjects and in Raynaud's disease. General Pharmacology 15: 107–113.PubMedCrossRef Kaada, B., E. Olsen, and O. Eielsen. 1984. In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation: III. Increase in plasma VIP in normal subjects and in Raynaud's disease. General Pharmacology 15: 107–113.PubMedCrossRef
25.
go back to reference Cosmo, P., H. Svensson, S. Bornmyr, and S. Wikström. 2000. Effects of transcutaneous nerve stimulation on the microcirculation in chronic leg ulcers. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 34: 61–64.PubMedCrossRef Cosmo, P., H. Svensson, S. Bornmyr, and S. Wikström. 2000. Effects of transcutaneous nerve stimulation on the microcirculation in chronic leg ulcers. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 34: 61–64.PubMedCrossRef
26.
go back to reference Cramp, A.F.L., C. Gilsenan, A.S. Lowe, and D.M. Walsh. 2000. The effect of high- and low-frequency transcutaneous electrical nevre stimulation upon cutaneous blood flow and skin temperature in healthy subjects. Clinical Physiology 20: 150–157.PubMedCrossRef Cramp, A.F.L., C. Gilsenan, A.S. Lowe, and D.M. Walsh. 2000. The effect of high- and low-frequency transcutaneous electrical nevre stimulation upon cutaneous blood flow and skin temperature in healthy subjects. Clinical Physiology 20: 150–157.PubMedCrossRef
27.
go back to reference Kloth, L.C., and J.M. McCulloch. 1996. Promotion of wound healing with electrical stimulation. Advances in Skin and Wound Care 9: 42–45. Kloth, L.C., and J.M. McCulloch. 1996. Promotion of wound healing with electrical stimulation. Advances in Skin and Wound Care 9: 42–45.
28.
go back to reference Sebastian, A., F. Syed, D. Perry, V. Balamurugan, J. Colthurst, I.H. Chaudhry, and A. Bayat. 2011. Acceleration of cutaneous healing by electrical stimulation: degenerate electrical waveform down-regulates inflammation, up-regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study. Wound Repair and Regeneration 19: 693–708.PubMedCrossRef Sebastian, A., F. Syed, D. Perry, V. Balamurugan, J. Colthurst, I.H. Chaudhry, and A. Bayat. 2011. Acceleration of cutaneous healing by electrical stimulation: degenerate electrical waveform down-regulates inflammation, up-regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study. Wound Repair and Regeneration 19: 693–708.PubMedCrossRef
29.
go back to reference Khalil, Z., and M. Merhi. 2000. Effects of aging on neurogenic vasodilator responses evoked by transcutaneous electrical nerve stimulation: relevance to wound healing. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 55: 257–263.CrossRef Khalil, Z., and M. Merhi. 2000. Effects of aging on neurogenic vasodilator responses evoked by transcutaneous electrical nerve stimulation: relevance to wound healing. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 55: 257–263.CrossRef
30.
go back to reference Liebano, R.E., L.E. Abla, and L.M. Ferreira. 2008. Effect of low-frequency transcutaneous electrical nerve stimulation (TENS) on the viability of ischemic skin flaps in the rat: an amplitude study. Wound Repair and Regeneration 16: 65–69.PubMedCrossRef Liebano, R.E., L.E. Abla, and L.M. Ferreira. 2008. Effect of low-frequency transcutaneous electrical nerve stimulation (TENS) on the viability of ischemic skin flaps in the rat: an amplitude study. Wound Repair and Regeneration 16: 65–69.PubMedCrossRef
31.
go back to reference Khalil, Z., and R.D. Helme. 1996. Sensory peptides as neuromodulators of wound healing in aged rats. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 51: 354–361.CrossRef Khalil, Z., and R.D. Helme. 1996. Sensory peptides as neuromodulators of wound healing in aged rats. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 51: 354–361.CrossRef
32.
go back to reference Barrientos, S., O. Stojadinovic, M.S. Golinko, H. Brem, and M. Tomic-Canic. 2008. Growth factors and cytokines in wound healing. Wound Repair and Regeneration 16: 585–601.PubMedCrossRef Barrientos, S., O. Stojadinovic, M.S. Golinko, H. Brem, and M. Tomic-Canic. 2008. Growth factors and cytokines in wound healing. Wound Repair and Regeneration 16: 585–601.PubMedCrossRef
33.
go back to reference Zhou, L.J., R. Matsui, and I. Ono. 2000. Development of a chronic skin defect model and a study of cytokine secretion using the model. Wound Repair and Regeneration 8: 304–318.PubMedCrossRef Zhou, L.J., R. Matsui, and I. Ono. 2000. Development of a chronic skin defect model and a study of cytokine secretion using the model. Wound Repair and Regeneration 8: 304–318.PubMedCrossRef
34.
go back to reference Mast, B.A., and G.S. Schultz. 1996. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair and Regeneration 4: 411–420.PubMedCrossRef Mast, B.A., and G.S. Schultz. 1996. Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Repair and Regeneration 4: 411–420.PubMedCrossRef
35.
go back to reference Mateo, R.B., J.S. Reichner, and J.E. Albina. 1994. Interleukin-6 activity in wounds. The American Journal of Physiology 266: 1840–1844. Mateo, R.B., J.S. Reichner, and J.E. Albina. 1994. Interleukin-6 activity in wounds. The American Journal of Physiology 266: 1840–1844.
36.
go back to reference Akira, S., and T. Kishimoto. 1992. IL-6 and NF-IL6 in acute-phase response and viral infection. Immunological Reviews 127: 25–50.PubMedCrossRef Akira, S., and T. Kishimoto. 1992. IL-6 and NF-IL6 in acute-phase response and viral infection. Immunological Reviews 127: 25–50.PubMedCrossRef
37.
go back to reference Lin, Z.Q., T. Kondo, Y. Ishida, T. Takayasu, and N. Mukaida. 2003. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. Journal of Leukocyte Biology 73: 713–721.PubMedCrossRef Lin, Z.Q., T. Kondo, Y. Ishida, T. Takayasu, and N. Mukaida. 2003. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. Journal of Leukocyte Biology 73: 713–721.PubMedCrossRef
38.
go back to reference Hübner, G., M. Brauchle, H. Smola, M. Madlener, R. Fässler, and S. Werner. 1996. Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice. Cytokine 8: 548–556.PubMedCrossRef Hübner, G., M. Brauchle, H. Smola, M. Madlener, R. Fässler, and S. Werner. 1996. Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice. Cytokine 8: 548–556.PubMedCrossRef
39.
go back to reference Locksley, R.M., N. Killeen, and M.J. Lenardo. 2001. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104: 487–501.PubMedCrossRef Locksley, R.M., N. Killeen, and M.J. Lenardo. 2001. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104: 487–501.PubMedCrossRef
40.
go back to reference Sainson, R.C., D.A. Johnston, H.C. Chu, M.T. Holderfield, M.N. Nakatsu, S.P. Crampton, J. Davis, E. Conn, and C.C. Hughes. 2008. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood 111: 4997–5007.PubMedCentralPubMedCrossRef Sainson, R.C., D.A. Johnston, H.C. Chu, M.T. Holderfield, M.N. Nakatsu, S.P. Crampton, J. Davis, E. Conn, and C.C. Hughes. 2008. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood 111: 4997–5007.PubMedCentralPubMedCrossRef
41.
go back to reference Cassatella, M.A. 1999. Neutrophil-derived proteins: selling cytokines by the pound. Advances in Immunology 73: 369–509.PubMedCrossRef Cassatella, M.A. 1999. Neutrophil-derived proteins: selling cytokines by the pound. Advances in Immunology 73: 369–509.PubMedCrossRef
42.
go back to reference Ries, C., V. Egea, M. Karow, H. Kolb, M. Jochum, and P. Neth. 2007. MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109: 4055–4063.PubMedCrossRef Ries, C., V. Egea, M. Karow, H. Kolb, M. Jochum, and P. Neth. 2007. MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109: 4055–4063.PubMedCrossRef
43.
go back to reference Grellner, W., T. Georg, and J. Wilske. 2000. Quantitative analysis of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in human skin wounds. Forensic Science International 113: 251–264.PubMedCrossRef Grellner, W., T. Georg, and J. Wilske. 2000. Quantitative analysis of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in human skin wounds. Forensic Science International 113: 251–264.PubMedCrossRef
Metadata
Title
Transcutaneous Electrical Nerve Stimulation (TENS) Accelerates Cutaneous Wound Healing and Inhibits Pro-inflammatory Cytokines
Authors
Seren Gülşen Gürgen
Oya Sayın
Ferihan Çetin
Ayşe Tuç Yücel
Publication date
01-06-2014
Publisher
Springer US
Published in
Inflammation / Issue 3/2014
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-013-9796-7

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