Abstract
Osteoarthritis (OA) triggers increased levels of inflammatory markers, including prostaglandin (PG) E2 and proinflammatory cytokines. The elevation of cytokine levels is closely associated with increased articular tissue degeneration. Thus, the use of combination therapies may presumably be able to enhance the effects on the modulation of inflammatory markers. The present study aimed to evaluate and compare the effects of photobiomodulation therapy (PBMT), physical exercise, and topical nonsteroidal anti-inflammatory drug (NSAID) use on the inflammatory process after they were applied either alone or in different combinations. OA was induced by intra-articular papain injection in the knee of rats. After 21 days, the animals began treatment with a topical NSAID and/or with physical exercise and/or PBMT. Treatments were performed three times a week for eight consecutive weeks, totaling 24 therapy sessions. Analysis of real-time polymerase chain reaction (RT-PCR) gene expression; interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) protein expression; and PGE2 levels by enzyme-linked immunosorbent assay (ELISA) was conducted. Our results showed that PBMT alone and Exerc + PBMT significantly reduced IL-1β gene expression (p < 0.05) while no treatment changed both IL-6 and TNF-α gene expression. Treatment with NSAID alone, PBMT alone, Exerc + PBMT, and NSAID + PBMT reduced IL-1β protein expression (p < 0.05). All therapies significantly reduced IL-6 and TNF-α protein expression (p < 0.05) compared with the OA group. Similarly, all therapies, except Exerc, reduced the levels of PGE2 (p < 0.05) compared with the OA group. The results from the present study indicate that treatment with PBMT is more effective in modulating the inflammatory process underlying OA when compared with the other therapies tested.
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References
Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656
Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ (2015) Osteoarthritis. Lancet 386:376–387
Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21:16–21
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H (2011) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7:33–42
Loeser RF, Goldring SR, Scanzello CR, Goldring MB (2012) Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 64:1697–1707
Goldring MB, Otero M (2011) Inflammation in osteoarthritis. Curr Opin Rheumatol 23:471–478
Krasnokutsky S, Samuels J, Abramson SB (2007) Osteoarthritis in 2007. Bull NYU Hosp Jt Dis 65:222–228
Verbruggen G, Wittoek R, Vander Cruyssen B, Elewaut D (2012) Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification. Ann Rheum Dis 71:891–898
Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, Conrozier T, Loeuille D, Kivitz AJ, Silver D, Appleton BE (2009) Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 61:344–352
Seed SM, Dunican KC, Lynch AM (2011) Treatment options for osteoarthritis: considerations for older adults. Hosp Pract 39:62–73
Pallotta RC, Bjordal JM, Frigo L, Leal Junior EC, Teixeira S, Marcos RL, Ramos L, Messias Fde M, Lopes-Martins RA (2012) Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation. Lasers Med Sci 27:71–78
Thomas JL (2013) Helpful or harmful? Potential effects of exercise on select inflammatory conditions. Phys Sportsmed 41:93–100
Alves AC, Vieira R, Leal-Junior EC, Dos Santos S, Ligeiro AP, Albertini R, Junior J, De Carvalho P (2013) Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Arthritis Res Ther 15:R116
Dos Santos SA, Alves AC, Leal-Junior ECP, Albertini R, Vieira RDeP, Ligeiro AP, Junior JA, De Carvalho PDeT (2014) Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and neutrophils and macrophages in acute joint inflammation. Lasers Med Sci 29:1051–1058
Murat N, Karadam B, Ozkal S, Karatosun V, Gidener S (2007) Quantification of papain-induced rat osteoarthritis in relation to time with the Mankin score. Acta Orthop Traumatol Turc 41:233–237
Lima WP, Carnevali LC Jr, Eder R, Costa Rosa LF, Bacchi EM, Seelaender MC (2005) Lipid metabolism in trained rats: effect of guaraná (Paullinia cupana Mart.) supplementation. Clin Nutr 24:1019–1028
Wang X, Liang J, Koike T, Sun H, Ichikawa T, Kitajima S, Morimoto M, Shikama H, Watanabe T, Sasaguri Y, Fan J (2004) Overexpression of human matrix metalloproteinase-12 enhances the development of inflammatory arthritis in transgenic rabbits. Am J Pathol 165:1375–1383
Milares LP, Assis L, Siqueira A, Claudino V, Domingos H, Almeida T, Tim C, Renno AC (2016) Effectiveness of an aquatic exercise program and low-level laser therapy on articular cartilage in an experimental model of osteoarthritis in rats. Connect Tissue Res
Assis L, Milares LP, Almeida T, Tim C, Magri A, Fernandes KR, Medalha C, Muniz Renno AC (2016) Aerobic exercise training and low-level laser therapy modulate inflammatory response and degenerative process in an experimental model of knee osteoarthritis in rats. Osteoarthr Cartil 24:169–177
Hamblin MR (2013) Can osteoarthritis be treated with light? Arthritis Res Ther 15(5):120
Wang P, Liu C, Yang X, Zhou Y, Wei X, Ji Q, Yang L, He C (2014) Effects of low-level laser therapy on joint pain, synovitis, anabolic, and catabolic factors in a progressive osteoarthritis rabbit model. Lasers Med Sci 29:1875–1885
Castano AP, Dai T, Yaroslavsky I, Cohen R, Apruzzese WA, Smotrich MH, Hamblin MR (2007) Low-level laser therapy for zymosan-induced arthritis in rats: importance of illumination time. Lasers Surg Med 39:543–550
Oshima Y, Coutts RD, Badlani NM, Healey RM, Kubo T, Amiel D (2011) Effect of light-emitting diode (LED) therapy on the development of osteoarthritis (OA) in a rabbit model. Biomed Pharmacother 65:224–229
Muniz Renno AC, de Moura FM, dos Santos NS, Tirico RP, Bossini PS, Parizotto NA (2006) The effects of infrared-830 nm laser on exercised osteopenic rats. Lasers Med Sci 21:202–207
Litalien C, Jacqz-Aigrain E (2001) Risks and benefits of nonsteroidal anti-inflammatory drugs in children: a comparison with paracetamol. Paediatr Drugs 3:817–858
Leal-Junior EC (2015) Photobiomodulation therapy in skeletal muscle: from exercise performance to muscular dystrophies. Photomed Laser Surg 33:53–54
Leal-Junior EC, Vanin AA, Miranda EF, de Carvalho PT, Dal Corso S, Bjordal JM (2015) Effect of phototherapy (low-level laser therapy and light-emitting diode therapy) on exercise performance and markers of exercise recovery: a systematic review with meta-analysis. Lasers Med Sci 30:925–939
Miranda EF, Vanin AA, Tomazoni SS, Grandinetti Vdos S, de Paiva PR, Machado Cdos S, Monteiro KK, Casalechi HL, de Tarso P, de Carvalho C, Leal-Junior EC (2016) Using pre-exercise photobiomodulation therapy combining super-pulsed lasers and light-emitting diodes to improve performance in progressive cardiopulmonary exercise tests. J Athl Train 51:129–135
Pinto HD, Vanin AA, Miranda EF, Tomazoni SS, Johnson DS, Albuquerque-Pontes GM, Aleixo Junior IO, Grandinetti VD, Casalechi HL, de Carvalho PT, Leal-Junior EC (2016) Photobiomodulation therapy (PBMT) improves performance and accelerates recovery of high-level rugby players in field test: a randomized, crossover, double-blind, placebo-controlled clinical study. J Strength Cond Res
Vanin AA, Miranda EF, Machado CS, de Paiva PR, Albuquerque-Pontes GM, Casalechi HL, de Tarso Camillo de Carvalho P, Leal-Junior EC (2016) What is the best moment to apply phototherapy when associated to a strength training program? A randomized, double-blinded, placebo-controlled trial: phototherapy in association to strength training. Lasers Med Sci
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Experimental protocol was approved by the Ethics Committee for Animal Experimentation (number 077, page 130, book 02) of the Institute of Biomedical Sciences, University of São Paulo (ICB-USP).
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Shaiane Silva Tomazoni would like to thank Sao Paulo Research Foundation—FAPESP for PhD scholarship (grant number 2011/18785-9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests
Professor Ernesto Cesar Pinto Leal-Junior receives research support from Multi Radiance Medical (Solon, OH, USA), a laser device manufacturer. Multi Radiance Medical had no role in the planning of this study, and the laser device used was not theirs. They had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors declare that they have no competing interests.
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Tomazoni, S.S., Leal-Junior, E.C.P., Pallotta, R.C. et al. Effects of photobiomodulation therapy, pharmacological therapy, and physical exercise as single and/or combined treatment on the inflammatory response induced by experimental osteoarthritis. Lasers Med Sci 32, 101–108 (2017). https://doi.org/10.1007/s10103-016-2091-8
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DOI: https://doi.org/10.1007/s10103-016-2091-8