Skip to main content

Advertisement

SpringerLink
Log in

Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase-induced tendinitis in rat

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Tendinopathies are directly related to unbalance in expression of pro- and anti-inflammatory cytokines which are responsible by degeneration process of tendinocytes. In the current study, we decided to investigate if LLLT could reduce mRNA expression for TNF-α, IL-1β, IL-6, TGF-β cytokines, and COX-2 enzyme. Forty-two male Wistar rats were divided randomly in seven groups, and tendinitis was induced with a collagenase intratendinea injection. The mRNA expression was evaluated by real-time PCR in 7th and 14th days after tendinitis. LLLT irradiation with wavelength of 780 nm required for 75 s with a dose of 7.7 J/cm2 was administered in distinct moments: 12 h and 7 days post tendinitis. At the 12 h after tendinitis, the animals were irradiated once in intercalate days until the 7th or 14th day in and them the animals were killed, respectively. In other series, 7 days after tendinitis, the animals were irradiated once in intercalated days until the 14th day and then the animals were killed. LLLT in both acute and chronic phases decreased IL-6, COX-2, and TGF-β expression after tendinitis, respectively, when compared to tendinitis groups: IL-6, COX-2, and TGF-β. The LLLT not altered IL-1β expression in any time, but reduced the TNF-α expression; however, only at chronic phase. We conclude that LLLT administered with this protocol reduces one of features of tendinopathies that is mRNA expression for pro-inflammatory mediators.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Khan KM, Cook JL, Kannus P, Maffulli N, Bonar SF (2002) Time to abandon the “tendinitis” myth. BMJ 324:626–627

    Article  CAS  PubMed  Google Scholar 

  2. Corps AN, Robinson AH, Movin T, Costa ML, Ireland DC, Hazelman BL et al (2004) Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies. Rheumatol (Oxf Print) 43:969–972

    Article  CAS  Google Scholar 

  3. Rees JD, Wilson AM, Wolman RL (2006) Current concepts in the management of tendon disorders. Rheumatol (Oxf Print) 45:508–521

    Article  CAS  Google Scholar 

  4. Smidt N, Lewis M, Hay EM, Van der Windt DA, Bouter LM, Croft P (2005) A comparison of two primary care trials on tennis elbow: issues of external validity. Ann Rheum Dis 64:1406–1409

    Article  CAS  PubMed  Google Scholar 

  5. Coleman BD, Khan KM, Maffulli N, Cook JL, Wark JD (2000) for the Victorian Institute of Sport Tendon Study Group. Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies. Scand J Med Sci Sports 10:2–11

    Article  CAS  PubMed  Google Scholar 

  6. Tallon C, Coleman BD, Khan KM, Maffulli N (2001) Outcome of surgery for chronic Achilles tendinopathy: a critical review. Am J Sports Med 29:315–320

    CAS  PubMed  Google Scholar 

  7. Fredberg U (2004) Tendinopathy—tendinitis or tendinosis? The question is still open. Scand J Med Sci Sports 14:270–272

    Article  PubMed  Google Scholar 

  8. Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM et al (2006) Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human Achilles tendon. Arthritis Rheum 54:832–842

    Article  CAS  PubMed  Google Scholar 

  9. Puddu G, Ippolito E, Postacchini F (1976) A classification of Achilles tendon disease. Am J Sports Med 4:145–150

    Article  CAS  PubMed  Google Scholar 

  10. Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL (1994) Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis. Ann Rheum Dis 53:367–376

    Article  CAS  PubMed  Google Scholar 

  11. Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL (1994) Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis 53:359–366

    Article  CAS  PubMed  Google Scholar 

  12. Riley G (2008) Tendinopathy—from basic science to treatment. Nature 4(2):82–89

    Google Scholar 

  13. Stone D, Green C, Rao U, Aizawa H, Yamaji T, Niyibizi C et al (1999) Cytokine-induced tendinitis: a preliminary study in rabbits. J Orthop Res 17:168–177

    Article  CAS  PubMed  Google Scholar 

  14. Chiu D, Ma K, Scott A, Duronio V (2005) Acute activation of Erk1/Erk2 and protein kinase B/akt proceed by independent pathways in multiple cell types. FEBS J 272:4372–4384

    Article  CAS  PubMed  Google Scholar 

  15. Hosaka Y, Kirisawa R, Ueda H, Yamaguchi M, Takehana K (2005) Differences in tumor necrosis factor (TNF)alpha and TNF receptor-1-mediated intracellular signaling factors in normal, inflamed and scar-formed horse tendons. J Vet Med Sci 67(10):985–991

    Article  CAS  PubMed  Google Scholar 

  16. Fredberg U, Ostgaard R (2008) Effect of ultrasound-guided, peritendinous injections of adalimumab and anakinra in chronic Achilles tendinopathy: a pilot study. Scand J Med Sci Sports. 2008, May 19

  17. Thampatty BP, Li H, Im HJ, Wang JH (2007) EP4 receptor regulates collagen type-I, MMP-1, and MMP-3 gene expression in human tendon fibroblasts in response to IL-1 beta treatment. Gene 386(1–2):154–161

    Article  CAS  PubMed  Google Scholar 

  18. Sivakumar B, Akhavani MA, Winlove CP, Taylor PC, Paleolog EM, Kang N (2008) Synovial hypoxia as a cause of tendon rupture in rheumatoid arthritis. J Hand Surg Am 33(1):49–58

    Article  PubMed  Google Scholar 

  19. Wang JH, Jia F, Yang G, Yang S (2003) Campbell BH, Stone D, Woo SL. Cyclic mechanical stretching of human tendon fibroblasts increases the production of prostaglandin E2 and levels of cyclooxygenase expression: a novel in vitro model study. Connect Tissue Res 44(3–4):128–133

    CAS  PubMed  Google Scholar 

  20. Longo UG, Ronga M, Maffulli N (2009) Achilles tendinopathy. Sports Med Arthrosc Rev 17(2):112–126

    Article  Google Scholar 

  21. Corps AN, Jones GC, Harrall RL, Curry VA, Hazleman BL, Riley GP (2008) The regulation of aggrecanase ADAMTS-4 expression in human Achilles tendon and tendon-derived cells. Matrix Biol 27(5):393–401

    Article  CAS  PubMed  Google Scholar 

  22. Moustakas A, Heldin CH (2009) The regulation of TGFbeta signal transduction. Development 136(22):3699–3714

    Article  CAS  PubMed  Google Scholar 

  23. Triantafillopoulos IK, Banes AJ, Bowman KF Jr, Maloney M, Garrett WE Jr, Karas SG (2004) Nandrolone decanoate and load increase remodeling and strength in human supraspinatus bioartificial tendons. Am J Sports Med 32:934–943

    Article  PubMed  Google Scholar 

  24. Downing DS, Weinstein A (1986) Ultrasound therapy of subacromial bursitis. A double blind trial. Phys Ther 66:194–199

    CAS  PubMed  Google Scholar 

  25. McLauchlan GJ, Handoll HH (2001) Interventions for treating acute and chronic Achilles tendinitis. Cochrane Database Syst Rev CD000232, 2001

  26. Hsu RW, Hsu WH, Tai CL, Lee KF (2004) Effect of hyperbaric oxygen therapy on patellar tendinopathy in a rabbit model. J Trauma 57:1060–1064

    Article  CAS  PubMed  Google Scholar 

  27. Wiley P (2002) Low energy extracorporeal shock-wave treatment for tendinitis of the supraspinatus (Abstract). Clin J Sport Med 12:262

    Article  PubMed  Google Scholar 

  28. Almekinders LC, Temple JD (1998) Etiology, diagnosis, and treatment of tendonitis: an analysis of the literature. Med Sci Sports Exerc 30:1183–1190

    Article  CAS  PubMed  Google Scholar 

  29. Bjordal JM, Lopes-Martins RAB, Iversen VV (2006) A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. Br J Sports Med 40:76–80

    Article  CAS  PubMed  Google Scholar 

  30. Demir H, Yaray S, Kirnap M et al (2004) Comparison of the effects of laser and ultrasound treatments on experimental wound healing in rats. J Rehabil Res Dev 41(5):721–728

    Article  PubMed  Google Scholar 

  31. Salate ACB, Barbosa G, Gaspar P et al (2005) Effect of In-Ga-Al-P diode laser irradiation on angiogenesis in partial ruptures of Achilles tendon in rats. Photomed Laser Surg 23(5):470–475

    Article  PubMed  Google Scholar 

  32. Carrinho PM, Renno ACM, Koeke P et al (2006) Comparative study using 685-nm and 830-nm lasers in the tissue repair of tenotomized tendons in the mouse. Photomed Laser Surg 24(6):754–758

    Article  PubMed  Google Scholar 

  33. Fillipin LI, Mauriz JL, Vedovelli K et al (2005) Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon. Lasers Surg Med 37:293–300

    Article  PubMed  Google Scholar 

  34. Badley EM, Tennant A (1993) Impact of disablement due to rheumatic disorders in a British population: estimates of severity and prevalence from the Calderdale Rheumatic Disablement Survey. Ann Rheum Dis 52:6–13

    Article  CAS  PubMed  Google Scholar 

  35. McCormick A et al (1995) Assessing health needs in primary care. Morbidity study from general practice provides another source of information. BMJ 310:1534

    CAS  PubMed  Google Scholar 

  36. Chard MD et al (1991) Shoulder disorders in the elderly: a community survey. Arthritis Rheum 34:766–769

    Article  CAS  PubMed  Google Scholar 

  37. Bamji AN et al (1990) What do rheumatologists do? A pilot audit study. Br J Rheumatol 29:295–298

    Article  CAS  PubMed  Google Scholar 

  38. Tumilty S, Munn J, McDonough S, Hurley DA, Basford JR, Baxter GD (2010) Low level laser treatment of tendinopathy: a systematic review with meta-analysis. Photomed Laser Surg 28(1):3–16

    Google Scholar 

  39. Bjordal JM, Lopes-Martins RA, Joensen J, Couppe C, Ljunggren AE, Stergioulas A, Johnson MI (2008) A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord 29;9:75

    Google Scholar 

  40. Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes-Martins RA (2006) Photoradiation in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg 24(2):158–168

    Article  CAS  PubMed  Google Scholar 

  41. Xavier M, Murilo Xavier, Débora Rodrigues David, Renato Aparecido de Souza, Arthur Nascimento Arrieiro, Humberto Miranda, Eduardo Tadeu Santana, José Antonio Silva JR, Regiane Albertini. Anti-inflammatory effects of low-level light emitting diode therapy on Achilles tendinitis in rats. Lasers Surg Med 2010 (Epub ahead of print)

  42. Dogan A, Korkmaz M, Cengiz N, Kalender AM, Gokalp MA (2009) Biomechanical comparison of Achilles tenotomy and achilloplasty techniques in young rats: an experimental study. J Am Podiatr Med Assoc 99(3):216–222

    PubMed  Google Scholar 

  43. Koeke PU, Parizotto NA, Carrinho PM, Salate AC (2005) Comparative study of the efficacy of the topical application of hydrocortisone, therapeutic ultrasound and phonophoresis on the tissue repair process in rat tendons. Ultrasound Med Biol 31(3):345–350

    Article  PubMed  Google Scholar 

  44. Brosseau L, Robinson V, Wells G, Debie R, Gam A, Harman K, Morin M, Shea B, Tugwell P (2007) Low level laser therapy (Classes III) for treating osteoarthritis. Cochrane Database Syst Rev 18(1):CD002046

    Google Scholar 

  45. Albertini R, Aimbire F, Villaverde AB, Silva JA Jr, Costa MS (2007) COX-2 mRNA expression decreases in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation after low level laser therapy. Inflamm Res 56(6):228–229

    Article  CAS  PubMed  Google Scholar 

  46. Albertini R, Villaverde AB, Aimbire F, Bjordal J, Brugnera A, Mittmann J, Silva JA, Costa M (2008) Cytokine mRNA expression is decreased in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation after low-level laser therapy. Photomed Laser Surg 26(1):19–24

    Google Scholar 

  47. Asundi KR, Rempel DM (2008) MMP-1, IL-1beta, and COX-2 mRNA expression is modulated by static load in rabbit flexor tendons. Ann Biomed Eng 36(2):237–243

    Article  PubMed  Google Scholar 

  48. Dunican AL, Leuenroth SJ, Grutkoski P et al (2000) TNFalpha-induced suppression of PMN apoptosis is mediated through interleukin-8 production. Shock 14:284–289

    Article  CAS  PubMed  Google Scholar 

  49. Aimbire F, Albertini R, Pacheco MT, Castro-Faria-Neto HC, Leonardo PS, Iversen VV, Lopes-Martins RA, Bjordal JM (2006) Low-level laser therapy induces dose-dependent reduction of TNFalpha levels in acute inflammation. Photomed Laser Surg 24(1):33–37

    Google Scholar 

  50. Garbacki N, Tits M, Angenot L et al (2004) Inhibitory effects of proanthocyanidins from Ribes nigrum leaves on carrageenin acute inflammatory reactions induced in rats BMC. BMC Pharmacol 4(1):1–25

    Article  Google Scholar 

  51. Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117:1162–1172

    Article  CAS  PubMed  Google Scholar 

  52. Fredberg U, Stengaard-Pedersen K (2008) Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports 18(1):3–15

    Article  CAS  PubMed  Google Scholar 

  53. Oliveira FS, Pinfildi CE, Parizoto NA, Liebano RE, Bossini PS, Garcia EB, Ferreira LM (2009) Effect of low level laser therapy (830 nm) with different therapy regimes on the process of tissue repair in partial lesion calcaneous tendon. Lasers Surg Med 41:271–276

    Article  PubMed  Google Scholar 

  54. O’Connor JP, Lysz T (2008) Celecoxib, NSAIDs and the skeleton. Drugs Today 44(9):693–709

    Article  PubMed  Google Scholar 

  55. Campana V, Moya M, Gavotto A, Juri H, Palma JA (1998) Effects of diclofenac sodium 8 and HeNe laser irradiation on plasmatic fibrinogen levels in inflammatory processes. J Clin Laser Med Surg 16(6):317–320

    CAS  PubMed  Google Scholar 

  56. Tsai WC, Hsu CC, Chou SW, Chung CY, Chen J, Pang JH (2007) Effects of celecoxib on migration, proliferation and collagen expression of tendon cells. Connect Tissue Res 48(1):46–51

    Article  CAS  PubMed  Google Scholar 

  57. Tsai WC, Hsu CC, Chen CP, Chen MJ, Lin MS, Pang JH (2006) Ibuprofen inhibition of tendon cell migration and down-regulation of paxillin expression. J Orthop Res 24(3):551–558

    Article  CAS  PubMed  Google Scholar 

  58. Bjordal JM, Klovning A, Ljunggren AE, Slørdal L (2007) Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: ameta-analysis of randomised placebo-controlled trials. Eur J Pain 11(2):125–138

    Article  CAS  PubMed  Google Scholar 

  59. Clark RAF, McCoy GA, Folkvord JM, McPherson JM (1997) TGF-beta 1 stimulates cultured human fibroblasts to proliferate and produce tissue-like fibroplasia: a fibronectin matrix-dependent event. J Cell Physiol 170:69–80

    Article  CAS  PubMed  Google Scholar 

  60. Shah M, Foreman DM, Ferguson MWJ (1995) Neutralisation of TGF-beta1 and b2 or exogenous addition of TGF-beta3 to cutaneous rat wounds reduces scarring. J Cell Sci 108:985–1002

    CAS  PubMed  Google Scholar 

  61. Ignotz RA, Massague J (1986) Transforming growth-factor beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261:4337–4345

    CAS  PubMed  Google Scholar 

  62. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM et al (1986) Transforming growth-factor type-beta rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83:4167–4171

    Article  CAS  PubMed  Google Scholar 

  63. Wang X, Smith P, Pu L, Kim YJ, Ko F, Robson MC (1999) Exogenous transforming growth factor beta(2) modulates collagen I and collagen III synthesis in proliferative scar xenografts in nude rats. J Surg Res 87:194–200

    Article  CAS  PubMed  Google Scholar 

  64. Fukumura K, Matsunaga S, Yamamoto T, Nagamine T, Ishidou Y, Sakou T (1998) Immunolocalization of transforming growth factor-betas and type I and type II receptors in rat articular cartilage. Anticancer Res 18:4189–4193

    CAS  PubMed  Google Scholar 

  65. Matsunaga S, Yamamoto T, Fukumurak K (1999) Temporal and spatial expressions of transforming growth factor betas and their receptors in epiphyseal growth plate. Int J Oncol 14:1063–1067

    CAS  PubMed  Google Scholar 

  66. Tedgui A, Mallat Z (2001) Anti-Inflammatory mechanisms in the vascular wall. Circ Res 88:877–887

    Article  CAS  PubMed  Google Scholar 

  67. Fenwick SA, Curry V, Harrall RL, Hazleman BL, Hackney R, Riley GP (2001) Expression of transforming growth factor-beta isoforms and their receptors in chronic tendinosis. J Anat 199:231–240

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the “Fundação de Amparo à Pesquisa do Estado de São Paulo” (FAPESP) for the grants numbers 2007/02596-7, under which this research was conducted.

Author information

Authors and Affiliations

  1. Institute of Research and Development, Av. Shishima Hifumi, 2911, Urbanova, CEP, 12.244-000, São José dos Campos, SP, Brazil

    Débora Pires

  2. Institute of Biomedical Engineering, Universidade Camilo Castelo Branco – UNICASTELO, Rodovia Presidente Dutra, km 138, 122470-004, São José dos Campos, São Paulo, Brazil

    Murilo Xavier, Flavio Aimbire & Regiane Albertini

  3. Department of Rehabilitation Sciences, UNINOVE, Rua Vergueiro, 235, São Paulo, SP, Brazil

    Tiago Araújo, José Antônio Silva Jr. & Regiane Albertini

Authors
  1. Débora Pires
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Murilo Xavier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiago Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José Antônio Silva Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Flavio Aimbire
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Regiane Albertini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Regiane Albertini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pires, D., Xavier, M., Araújo, T. et al. Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase-induced tendinitis in rat. Lasers Med Sci 26, 85–94 (2011). https://doi.org/10.1007/s10103-010-0811-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10103-010-0811-z

Keywords

Search

Navigation