High Intensity Laser Therapy in Chronic Achilles Tendonitis

Single blind, randomized control study ^{(in press – uncorrected proof})

Authors: Prouza, O.^1,3, Jenicek, J.², Prochazka, M.³

Affiliations:

¹Department of Anatomy and Biomechanics, Faculty of Physical Education and Sports, Charles University in Prague

²Department of Rehabilitation Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague

³Rehab Clinic Jarov – Rehabilitation center

BACKGROUND: Chronic Achilles tendonitis is a painful condition generally caused by overuse and there are often unsatisfactory results with conservative treatment.
Abstract:

OBJECTIVE: The aim of the current study was to evaluate High Intensity Laser Therapy (class 4) in the treatment of chronic Achilles tendonitis. High intensity laser therapy is hypothesized to be effective and non-invasive therapeutic modality for this pathology.

DESIGN: The study was designed as a single blind, randomized control study.

SETTING: The study was conducted in a private rehabilitation facility – Rehab Clinic Jarov during the time interval June 2012 – May 2013.

PATIENTS: Fifty-one patients with chronic Achilles tendonitis were randomly assigned to a treatment group or a control group.

INTERVENTION: Both groups received equal therapy protocol consisting of 8 high intensity laser tre- atments over a period of 4 consecutive weeks. Placebo group received sham therapy with only navigation light emitted during the procedure.

MEASUREMENTS: Outcome measures were the visual analog scale (VAS), providing commonly used ra- ting of pain intensity, and a standardized ADL questionnaire.

RESULTS: The statistical data analysis in both observed parameters suggest significantly higher efficacy in

the HIL therapy group compared to placebo group at 4th and 12th week.

CONCLUSIONS: Patients diagnosed with CAT showed greater reduction in pain and improvement in ADL functional abilities after 8 high intensity laser treatment sessions than did patients receiving placebo thera- py. Based on the data analysis HIL therapy can be recommended as effective conservative clinical modality for chronic Achilles tendinopathy.

Introduction:

Chronic Achilles tendinopathy is a common disa- bility of the foot during walking and running.

Avoidance of painful activities, correction of misa- lignment by arch support, stretching exercises, and eccentric training combined with non-steroidal an- ti-inflammatory pain killers are the standard tre- atment regimen [1]. However, there is little evi- dence to support any effect of these modalities [2].

The effects of laser radiation for the regeneration of pathologically changed or traumatized tissue, suppressing inflammation and inflammation swe-

lling, and pain release were researched from the invention of the first laser devices in the 60s. Re- cent technological development enables the use of lasers with various wavelengths and intensity for the purpose of affecting their therapeutic effects.

Jointly with the clinical use of the first high-in- tensity lasers in invasive medicine, the research describing the bio-stimulation effects of low in- tensity lasers (cold, low level laser therapy) with intensity up to 500 mW begin to emerge in the second half of the 60s. The effect was explained by the laser radiation absorption at the cell level,

when the photon energy produces photochemical changes similar to the photosynthetic processes in plant cells [7] [8]. The medical use of biomodu- lating effects of the low-level lasers (i.e. low-le- vel laser therapy – LLLT) has quickly expanded from the 70s particularly in the East European countries; it earned greater popularity worldwide during the 80s, probably due to geopolitical divisi- on and insufficient literature in English language. During the period, new technologies emerged ena- bling the construction of significantly cheaper and smaller semi-conductive diode lasers with greater spectrum of emitted wavelengths which formed a prerequisite for wider clinical laser use in almost all areas within physical medicine [9] [4]. From the end of the 90s, lasers with performance at Watt level (high intensity laser, Class 4 laser) begin to emerge in the basic research and later in clinical rehabilitation practice. The technology  enables  to generate intensity commonly around 10W and more, for the purpose of producing stronger bio- modulation and analgesic effect. Despite their inclusion among class 4 lasers, the tissue damage cannot occur due to their strongly divergent cha- racter. The main contribution of this technology is a significant acceleration of the emission which enables significant increase of therapeutic dosage (J/cm²) without application time prolongation. Further effects of the high intensity laser include immediate analgesic and myo-relaxation  effects in pulsed application and also adjuvant thermal effect [10] [11] [12] [13] [14]. Currently, there are two basic technologies of high intensity laser for rehabilitation purposes: Modified invasive laser (NdYAG), and diode laser with high intensity. The advantage of NdYAG devices is the possibility to emit very high intensity at kWatt level but only  in extremely short pulses. Their restrictions then include the impossible continual emission, signi- ficant dimensions, and less economical operation. Diode lasers enable continual and pulsed emissi- on, flexibility within the used wavelengths and more acceptable device dimensions. Relative di- sadvantage is the inability to reach extremely high peak values in pulsed emissions. [12]

Clinical evidence:

Clinical studies of LLLT effectiveness published during both decades at the turn of the millennium, generally conform to the findings from the labo- ratory experiments, however, there is a number  of studies incompliant with the clinical effecti- veness. This fact is, however, in accordance with the knowledge of laser light action in tissue. Low intensity laser light is mostly absorbed in the su- perficial tissue layers. Therefore in some cases it is difficult to reach comparable therapeutic dose during studies in-vitro and in-vivo [25]. Recent- ly, the approach changes as regards this focus, and PEDro database for Evidence Based Medicine in Physiotherapy in 2010 registered almost one hun- dred randomized, controlled studies with accepta- ble methodological quality as per the scale PEDro [25]. Positive LLLT effect has been documented in particular in osteoarthritis treatment and other chronic  joint  disorders  [26]  [27]  [28]  [29] [30]

[31], rheumatoid disorders [30] [32], tendinopathy

[33] [34] [4] [35], radiculopathy [36] [37], neck

spine pains [38] [39], [40] [41] [42], fibromyal- gia [43], peripheral nerve disorders [44], healing wounds and scars [15] [7] [20] [45] [46] [47]. It is obvious the LLLT is a method currently very well clinically documented, however with clearly spe- cified physical limits (in particular maximum out- put limiting the depth of the tissue penetration, and the limited possibility to increase the therapeutic dosage). In relation to the restrictions, recently the lasers with higher intensity are currently used. It enables to influence very deep structures and in- tense increase of therapeutic dosage [11] [12]. Maximum therapeutic dose in LLLT is still discu- ssed, however does not usually exceed 16 J/cm² [12], in high intensity laser therapy the common dosage is usually around 80-120 J/cm². Despite the dogma of low intensity laser therapy, no inhibition effects occur with this significant increase of the therapeutic dosage. In the contrary the results with increased therapeutic dosage confirm increased clinical effectiveness [11] [13] [53] [12]. High in- tensity laser therapy is currently in the phase of dramatic development, when many clinical studies focusing on the effects are in progress. Intense ba- sic research taking place in particular in former de- cades confirmed the effective mechanisms of HIL not only in surface soft tissues [54] [55] [56] but also in osseous and cartilaginous tissue [57] [58]

[59] [60] [61]. Clinical studies currently published confirm the effects in symptomatic treatment o

pain [53] [14] [13], low back pain [62], effects on muscular micro-circulation [63] and impingement syndrome [64]. The first results of extensive cli- nical studies were currently published by Navrá- til [10] [11]. This author analyses the effects of diode lasers at high intensity in comparison with low intensity lasers in various chronic disorders of musculoskeletal apparatus. He describes indis- putably better results in lasers with intensity over 1W, and also mentions significant treatment period reduction. These statements are confirmed by Pro- cházka, who is the pioneer of using this technolo- gy in the Central Europe region [12] [65]. Further clinical studies confirm potential utilization of the intensity lasers in dermatological indications [66] [67] [68].

Materials and methods:

Consecutive outpatients attending the Rehab Cli- nic Jarov, from June 2012 to May 2013 were invi- ted to participate in the study. Diagnostic criteria for CAT were moderate to severe posterior heel pain located at the bone-tendon junction, exten- ding ≤2 cm proximally from the base of the heel, with swelling and impaired function. Patients had experienced Achilles tendon pain for at least 5 months before the study. A prior ultrasound stu- dy was performed if necessary in order to exclude the presence of any partial lesions of the tendon. Patients were excluded from the study if they met any of the following criteria: history of Achilles tendon surgery or local anesthetic and/or cortico- steroid injection administered within the previous 4 weeks. Written informed consent was obtained from all subjects.

Total of 51 were included in the study baseline. 49 patients (19 women, 30 men; mean age 48,1 years, SD=9.0, range 34-65) underwent the complete stu- dy protocol, 2 patients did not fulfill the complete assessment protocol. These two patients were not included in the statistical analysis. The included patients were randomly assigned into two groups: therapy group (n=24) and placebo group (n=25). The study design was based as a randomized, sin- gle-blind study.

Both groups received equal therapy protocol con- sisting of 8 high intensity laser treatments during 4 week interval. The course of treatment was the use of infrared laser of 1064 nm wavelength, the BTL

– 6000 High Intensity Laser 12W system (BTL In-

dustries Ltd.) was used. Patients were placed in a prone position on the treatment couch with hip and knee extended and the ankle in maximal extension. Placebo group received sham therapy when only navigation light was emitted during the therapy procedure. The therapy group received complete therapy protocol with average dosage of 100J/cm². The protocol consisted of two subsequent appli- cation phases, so called analgesic and biostimula- tive. First the area was treated with laser in pulsed mode, t=2-4 minutes, P=8 W, f= 25 Hz, DF=25

%. Second, a thermic, continuous mode was used with power ranging from 4 to 10W, depending on patients’ reactions. A standard handpiece equipped with a 30 mm spacer was used to ensure the same distance to the skin and verticality to the treated zone. An experienced physiotherapist provided HIL therapy. The time to apply both stages was 5-10 minutes.

All the patients were clinically assessed by a phy- sician three times: before the first therapy session, at week 4th and at week 12th (2 months follow-

-up) by the same tester. Assessment comprised out of VAS evaluation and standardized ADL questi- onnaire. Patients received no other physical thera- py intervention for the Achilles tendon during the study.

Following tests were performed during the evalua- tions:

- VAS at rest – for pain level evaluation (1- 10 levels, 1 – minimal pain, 10 – unbearable pain)

- ADL questionnaire – for evaluation of eventual restriction in the Activities of Daily Li- ving (social life, sport, work etc. Max points 150

– no restriction, 0 full limitation in all tested acti- vities)

Visual Analogue Scale (VAS) is a measu- rement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. For example, the amount of pain that a patient

feels ranges across a continuum from none to an extreme amount of pain. From the patient‘s perspective this spectrum appears continuous ± their pain does not take dis- crete jumps, as a categorization of none, mild, moderate and severe would suggest. It was to capture this idea of an underly- ing continuum that the VAS was devised. Operationally a VAS is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end, as illustrated in Fig. 1. The patient marks on the line the point that they feel represents their per- ception of their current state. The VAS score is determined by score from 1 to 10 representing related painful sensations of the patient. There are many other ways in which VAS have been presented, including vertical lines and lines with extra descrip- tors. Wewers & Lowe (1990) provide an informative discussion of the benefits and shortcomings of different styles of VAS. As such an assessment is clearly subjective, these scales are of most value when lo- oking at change within individuals, and are of less value for comparing across a group of individuals at one time point.

The statistical analysis was done separately for the two groups in order to evaluate the effects of HIL therapy. All analyses were performed using SPSS for Windows statistical software (version 18). Frequency distributions as well as means and standard deviations were used for descriptive pur- poses. At the baseline, differences in age and time since the onset of pain between treatment groups were analyzed with an independent 2-sample t test and a Wilcoxon rank-sum test, respectively.

Repeated measurements obtained before and after

treatments within groups were analyzed with a paired matched t test. A 2-way repeated measures analysis of variance (ANOVA) was performed to estimate differences between (group effect) and within treatment groups for each studied out- come. A Mann–Whitney test was used to compare between the same measurement interval (4 and

8 weeks) in groups in case of statistical signifi- cance. The alpha level for significance was set at 0,05.

Results:

The present study started with 51 patients. Two patients were excluded from the study. Tables 1 and 2 summarize test performance at the baseline and at the ensuing measurements for each tre- atment group. Statistically significant change in both ADL and VAS test performance was found in the HIL group but not in the control group.

Picture 1 – VAS evaluation – graphic results. VAS at rest

– for pain level evaluation (1-10 levels, 1-minimal, 10-un- bearable pain)

Table 1 - VAS evaluation. VAS at rest – for pain level valua- tion (1-10 levels, 1-minimal, 10-unbearable pain)

Picture 2 – ADL questionnaire – graphic results. For evaluation of eventual restriction in the Activities of Daily Living (social life, sport, work etc. Max points 150 – no restriction, 0 – full limitation in all tested activities)

Table 2 – ADL questionnaire. For evaluation of eventu- al restriction in the Activities of Daily Living (social life, sport, work etc. Max points 150 – no restriction, 0 – full limitation in all tested activities)

Discussion:

In this study we compared the results obtained after 8 treatment sessions over a period of 4 consecutive weeks with high intensity laser and placebo therapy in chronic Achilles tendonitis. The subjects treated with HIL proved a greater reduction of pain and a significant improvement in activities of daily living than the subjects treated with placebo. A possible explanation

of the laser effect is through an increase in the activity of mitochondrial enzymes and inflam- matory cytokines level affection. From the first description of the laser bio-stimulation in 1967 by Endre Mester, many laboratory in vitro studies and animal studies were published explaining

the mechanisms and theoretic background of the LLLT effects [13] [14] [15]. Specific parts of the cellular mitochondrial chains have the ability to absorb specific wavelength of laser radiation, and the release of other signal molecules (NO, cytoki- nes, growth factors) results in increased formation

of ATP, increasing the level of cellular metaboli- sm resulting in the tissue regeneration and hea- ling [16] [17] [18] [19] [4] [15] [20]. The studies indicate that laser radiation affects also increased fibroblastic activity, collagen synthesis, and an- giogenesis due to the endothelial cell proliferation in the tissue affected [21] [22] [23]. The effects on suppression of the inflammation were proven by inhibiting the in anti-inflammatory cytokines (interleukins, etc.) in the tissue, and pain release is explained indirectly by suppressing the inflam- mation and swelling, and directly by stimulating the secretion of endogenous opiates – endorphins and encephalins, and reducing the distribution speed in Aδ and C nerve fibers [24] [19].

Results of both observed parameters show sig- nificantly better results in HIL group above the placebo group. This fact proves the suitability of HIL therapy for the evaluated indications.

References:

[1] Wilson J J, Best T M. Common overuse tendon pro- blems:A review and recommendations for treatment. Am Fam Physician 2005; 72: 811-8.

[2] McLauchlan G J, Handoll H H. Intervention for treating acute and chornic Achilles tendonitis. Cochrane Database Syst Rev 2:CD000232, 2001.

[3] T. H. Maiman, „Stimulated optical radiation in ruby,“

1960.

[4] S. Tumilty, J. Munn, S. McDonough, D. A. Hurley, J.

R. Basford a G. D. Baxter, „Low level laser treatment of tendino- pathy: a systematic review with meta-analysis,“ Photomedicine and laser surgery, sv. 28, č. 1, pp. 3-16, 2010.

[5] W. J. Kneebone, D. CNC a D. FIAMA, „Practical appli- cations of low level laser therapy,“ Practical Pain Management, sv. 6, č. 8, pp. 34-40, 2006.

[6] Z. Simunovic, Lasers in Medivine and Dentistry: Basic science and up-to-date clinical application of Low Energy-Level Laser Therapy - LLLT, Z. Simunovic, Editor, Vitagraf, Rijeka, 2000.

[7] Y.-Y. Huang, A. C.-H. Chen, J. D. Carroll a M. R. Ham- blin, „Biphasic dose response in low level lightherapy,“ Dose-Re- sponse, sv. 7, č. 4, pp. 358-383, 2009.

[8] M. Devor, „What‘s in a laser beam for pain therapy?,“

Pain, sv. 43, č. 2, p. 139, 1990.

[9] H. T. Whelan, R. L. Smits Jr, E. V. Buchman, N. T. Whelan, S. G. Turner, D. A. Margolis, V. Cevenini, H. Stinson,

R. Ignatius a T. Martin, „Effect of NASA light-emitting diode irradiation on wound healing,“ Journal of clinical laser medicine

\& surgery, sv. 19, č. 6, pp. 305-314, 2001.

[10] K. P. V. J. H. S. B. E. N. V. Navrátil L., „Přínos HILT pro léčbu některých onemocnění pohybového aparátu,“ v XXII. Konference rehabilitační, fyzikální a balneo medicíny Jáchymov, 2012.

[11] K. P. V. J. H. S. B. E. N. V. Navrátil L., „The benefits of high performance laser beams in the treatment of musculoskeletal issues,“ Laser Florence 2012 - Lasers in Medical Science, sv. 27, pp. 1107-1142, 2012.

[12] M. Prochazka, Class IV. Laser in Non-invasive Laser

Therapy – clinical experience, 2006.

[13] N. Tiglič-Rogoznica, D. Stamenkovič, L. Frlan, V. Avan- cini-Dobrovič a T. Schnurrer-Luke Vrbanič, „Analgesic Effect of High Intensity Laser Therapy in Knee Osteoarthritis,“ Collegium

Antropologicum, sv. 35, č. 2, pp. 183-185, 2011.

[1] YASUO I., „Phototherapy for Chronic Pain Treatment,“ 2009.

[2] E. Mester, „Clinical results of wound-healing stimulati- on with laser and experimental studies of the action mechanism,“ Laser, sv. 75, pp. 119-125, 1976.

[3] A. P. Sommer, A. L. Pinheiro, A. R. Mester, R.-P. Franke a H. T. Whelan, „Biostimulatory windows in low-intensity laser activation: lasers, scanners, and NASA‘s light-emitting diode array system,“ Journal of clinical laser medicine \& surgery, sv.  19, č. 1, pp. 29-33, 2001.

[4] T. Karu a S. Kolyakov, „Exact action spectra for cellular responses relevant to phototherapy,“ Photomedicine and Laser Therapy, sv. 23, č. 4, pp. 355-361, 2005.

[5] C.-H. Chen, J.-L. Tsai, Y.-H. Wang, C.-L. Lee, J.-K. Chen a M.-H. Huang, „Low-level laser irradiation promotes cell proliferation and mRNA expression of type I collagen and decorin in porcine achilles tendon fibroblasts In Vitro,“ Journal of Ortho- paedic Research, sv. 27, č. 5, pp. 646-650, 2009.

[6] P. V. Peplow, T.-Y. Chung a G. D. Baxter, „Laser pho- tobiomodulation of proliferation of cells in culture: a review of human and animal studies,“ Photomedicine and Laser Surgery, sv. 28, č. S1, pp. 3-40, 2010.

[7] P. Peplow, T.-Y. Chung a G. Baxter, „Application of low level laser technologies for pain relief and wound healing:

overview of scientific bases,“ Physical Therapy Reviews, sv. 15, č.

4, pp. 253-285, 2010.

[8] T. Karu, „Photobiology of low-power laser effects,“

Health Phys, sv. 56, č. 5, pp. 691-704, 1989.

[9] T. I. Karu, Ten Lectures on Basic Science of Laser Pho- totheraphy, Prima Books, 2007.

[10] T. I. Karu, „Mitochondrial mechanisms of laser photo- therapy,“ v Proceedings of Light-Activated Tissue Regeneration and Therapy Conference, Lecture Notes in Electrical Engineering, 2008.

[11] L. Gavish, L. S. Perez, P. Reissman a S. D. Gertz, „Irra- diation with 780 nm diode laser attenuates inflammatory cytokines but upregulates nitric oxide in lipopolysaccharideâ€?stimulated macrophages: Implications for the prevention of aneurysm progre- ssion,“ Lasers in surgery and medicine, sv. 40, č. 5, pp. 371-378, 2008.

[12] J. T. Hopkins, T. A. McLoda, J. G. Seegmiller a G. D. Baxter, „Low-level laser therapy facilitates superficial wound healing in humans: a triple-blind, sham-controlled study,“ Journal of Athletic Training, sv. 39, č. 3, p. 223, 2004.

[13] J. Bjordal, R. Lopes-Martins a V. Iversen, „A randomi- sed, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendi- nous prostaglandin E2 concentrations,“ British journal of sports medicine, sv. 40, č. 1, pp. 76-80, 2006.

[14] C.-H. Chen, H.-S. Hung a S.-h. Hsu, „Low-energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway,“ Lasers in surgery and medicine, sv. 40, č. 1, pp. 46-54, 2008.

[15] C. S. Enwemeka, J. C. Parker, D. S. Dowdy, E. E. Hark- ness, L. E. Harkness a L. D. Woodruff, „The efficacy of low-po- wer lasers in tissue repair and pain control: a meta-analysis study,“ Photomedicine and Laser Therapy, sv. 22, č. 4, pp. 323-329, 2004.

[16] P. V. Peplow, T.-Y. Chung a G. D. Baxter, „Laser photo- biomodulation of wound healing: a review of experimental studies in mouse and rat animal models,“ Photomedicine and Laser Surge- ry, sv. 28, č. 3, pp. 291-325, 2010.

[17] J. M. Bjordal, R. A. Lopes-Martins, J. Joensen a V. Iversen, „The anti-inflammatory mechanism of low-level laser the- rapy and its relevance for clinical use in physiotherapy,“ Physical Therapy Reviews, sv. 15, č. 4, pp. 286-293, 2010.

[18] V. O. Fukuda, T. Y. Fukuda, M. Guimares, S. Shiwa, B.

D. C. d. Lima, R. A. B. L. Martins, R. A. Casarotto, P. P. Alfredo,

J. M. Bjordal a P. M. M. B. Fucs, „Short-term efficacy of low-le- vel laser therapy in patients with knee osteoarthritis: a randomized

placebo-controlled, double-blind clinical trial,“ Revista Brasileira

de Ortopedia, sv. 46, č. 5, pp. 526-533, 2011.

[1] J. M. Bjordal, C. Couppé, R. T. Chow, J. Turner a E. A. Ljunggren, „A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders,“ Aus- tralian Journal of Physiotherapy, sv. 49, č. 2, pp. 107-122, 2003.

[2] J. Bjordal, M. Johnson, R. Lopes-Martins, B. Bogen, R. Chow a A. Ljunggren, „Short-term efficacy of physical interventi- ons in osteoarthritic knee pain. A systematic review and meta-ana- lysis of randomised placebo-controlled trials,“ BMC Musculoske- letal Disorders, sv. 8, č. 1, p. 51, 2007.

[3] F. Tascioglu, O. Armagan, Y. Tabak, I. Corapci a C. Oner, „Low power laser treatment in patients with knee osteoar- thritis,“ Swiss Medical Weekly, sv. 134, č. 17-18, pp. 254-258, 2004.

[4] L. Brosseau, V. Robinson, G. Wells, R. DeBie, A. Gam,

K. Harman, M. Morin, B. Shea a P. Tugwell, „Low level laser therapy (Classes I, II and III) for treating osteoarthritis,“ The Cochrane Library, 2006.

[5] P. Conti, „Low level laser therapy in the treatment of temporomandibular disorders (TMD): a double-blind pilot study.,“ Cranio: the journal of craniomandibular practice, sv. 15, č. 2, p. 144, 1997.

[6] G. Bálint, K. Barabás, Z. Zeitler, J. Bakos, K. A. Kékesi, Á. Pethes, E. Nagy, T. Lakatos, P. V. Bálint a Z. Szekanecz, „Ex Vivo Soft-Laser Treatment Inhibits the Synovial Expression of Vimentin and Enolase, Potential Autoantigens in Rheumatoid Arthritis,“ Physical Therapy, sv. 91, č. 5, pp. 665-674, 2011.

[7] J. M. Bjordal, R. A. Lopes-Martins, J. Joensen, C. Couppe, A. E. Ljunggren, A. Stergioulas a M. I. Johnson, „A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendinopathy (tennis elbow),“ BMC Musculoskeletal Disorders, sv. 9, č. 1, p. 75, 2008.

[8] B. K. Coombes, L. Bisset a B. Vicenzino, „A new inte- grative model of lateral epicondylalgia,“ British journal of sports medicine, sv. 43, č. 4, pp. 252-258, 2009.

[9] D. I. Stasinopoulos a M. I. Johnson, „Effectiveness of low-level laser therapy for lateral elbow tendinopathy,“ Photome- dicine and Laser Therapy, sv. 23, č. 4, pp. 425-430, 2005.

[10] L. M. Konstantinovic, M. R. Cutovic, A. N. Milova- novic, S. J. Jovic, A. S. Dragin, M. D. Letic a V. M. Miler, „Low Level Laser Therapy for Acute Neck Pain with Radiculopathy: A Double Blind Placebo Controlled Randomized Study,“ Pain Medicine, sv. 11, č. 8, pp. 1169-1178, 2010.

[11] M. Jovičić, L. Konstantinović, M. Lazović a V. Jovičić,

„Clinical and functional evaluation of patients with acute low back pain and radiculopathy treated with different energy doses of low level laser therapy,“ Vojnosanitetski pregled, sv. 69, č. 8, pp. 656- 662, 2012.

[12] R. T. Chow, M. I. Johnson, R. A. Lopes-Martins a J. M. Bjordal, „Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials,“ The Lancet, sv. 374, č. 9705, pp. 1897-1908, 2009.

[13] A. R. Gross, C. Goldsmith, J. L. Hoving, T. Haines, P. Peloso, P. Aker, P. Santaguida a C. Myers, „Conservative man- agement of mechanical neck disorders: a systematic review.,“ The Journal of rheumatology, sv. 34, č. 5, pp. 1083-1102, 2007.

[14] G. E. Djavid, R. Mehrdad, M. Ghasemi, H. Hasan-

-Zadeh, A. Sotoodeh-Manesh a G. Pouryaghoub, „In chronic low back pain, low level laser therapy combined with exercise is more beneficial than exercise alone in the long term: a randomised tri- al,“ Australian Journal of Physiotherapy, sv. 53, č. 3, p. 155, 2007.

[15] R. Yousefi-Nooraie, E. Schonstein, K. Heidari, A.

Rashidian, V. Pennick, M. Akbari-Kamrani, S. Irani, B. Shakiba,

S. Mortaz Hejri a S. Mortaz Hejri, „Low level laser therapy for nonspecific low-back pain,“ Cochrane Database Syst Rev, sv. 2, 2008.

[16] S. Momenzadeh, F. H. Kiabi, M. Moradkhani a M. H. Moghadam, „Low Level Laser Therapy (LLLT) Combined with

Physical Exercise, A More Effective Treatment in Low Back Pain,“ Journal of Lasers in Medical Sciences Volume, sv. 3, č. 2, 2012.

[1] O. Armagan, F. Tascioglu, A. Ekim a C. Oner, „Long-

-term efficacy of low level laser therapy in women with fibromyal- gia: a placebo-controlled study,“ Journal of Back and Musculoske- letal Rehabilitation, sv. 19, č. 4, pp. 135-140, 2006.

[2] S. Rochkind, S. Geuna a A. Shainberg, „Phototherapy in peripheral nerve injury: effects on muscle preservation and nerve regeneration,“ International review of neurobiology, sv. 87, pp. 445-464, 2009.

[3] M. J. Conlan, J. W. Rapley a C. M. Cobb, „Biostimula- tion of wound healing by low-energy laser irradiation A review,“ Journal of clinical periodontology, sv. 23, č. 5, pp. 492-496, 2005.

[4] L. D. Woodruff, J. M. Bounkeo, W. M. Brannon, K. S. Dawes, C. D. Barham, D. L. Waddell a C. S. Enwemeka, „The efficacy of laser therapy in wound repair: a meta-analysis of the literature,“ Photomedicine and laser surgery, sv. 22, č. 3, pp. 241- 247, 2004.

[5] M. Kawecki, T. Bernad-Wisniewska, S. Sakiel, M. No- wak a A. Andriessen, „Laser in the treatment of hypertrophic burn scars,“ International Wound Journal, sv. 5, č. 1, pp. 87-97, 2008.

[6] Y. Ide, „Phototherapy for chronic pain treatment,“ Ma- sui. The Japanese journal of anesthesiology, sv. 58, č. 11, p. 1401, 2009.

[7] D. H. Hawkins a H. Abrahamse, „Time-dependent responses of wounded human skin fibroblasts following photothe- rapy,“ Journal of Photochemistry and Photobiology B: Biology, sv. 88, č. 2, pp. 147-155, 2007.

[8] D. H. Evans a H. Abrahamse, „Efficacy of three dif- ferent laser wavelengths for in vitro wound healing,“ Photoder- matology, Photoimmunology \& Photomedicine, sv. 24, č. 4, pp. 199-210, 2008.

[9] R. Jayasree, A. Gupta, K. Rathinam, P. Mohanan a M. Mohanty, „The influence of photodynamic therapy on the wound healing process in rats,“ Journal of biomaterials applications, sv. 15, č. 3, pp. 176-186, 2001.

[10] R. A. Franco, J. R. Dowdall, K. Bujold, C. Amann, W. Faquin, R. W. Redmond a I. E. Kochevar, „Photochemical repair of vocal fold microflap defects,“ The Laryngoscope, sv. 121, č. 6, pp. 1244-1251, 2011.

[11] P. K. Holden, C. Li, V. Da Costa, C. Sun, S. V. Bryant,

D. M. Gardiner a B. J. Wong, „The effects of laser irradiation of cartilage on chondrocyte gene expression and the collagen

matrix,“ Lasers in surgery and medicine, sv. 41, č. 7, pp. 487-491,

2009.

[12] A. Zati, G. Desando, C. Cavallo, R. Buda, S. Gianni- ni, D. Fortuna, A. Facchini a B. Grigolo, „Treatment of human cartilage defects by means of Nd: YAG Laser Therapy.,“ Journal of biological regulators and homeostatic agents, sv. 26, č. 4, pp. 701-711, 2011.

[13] P. Vescovi, E. Merigo, M. Manfredi, M. Meleti, C. Fornaini, M. Bonanini, J. P. Rocca a S. Nammour, „Nd: YAG laser biostimulation in the treatment of bisphosphonate-associated oste- onecrosis of the jaw: clinical experience in 28 cases,“ Photomedi- cine and laser surgery, sv. 26, č. 1, pp. 37-46, 2008.

[14] I. S. Kim, T. H. Cho, K. Kim, F. E. Weber a S. J. Hwang,

„High power pulsed Nd: YAG laser as a new stimulus to induce BMP2 expression in MC3T3E1 osteoblasts,“ Lasers in surgery and medicine, sv. 42, č. 6, pp. 510-518, 2010.

[15] P. Fiore, F. Panza, G. Cassatella, A. Russo, V. Frisardi,

V. Solfrizzi, M. Ranieri, L. Di Teo a A. Santamato, „Short-term effects of high-intensity laser therapy versus ultrasound therapy in the treatment of low back pain: a randomized controlled trial,“ Eur J Phys Rehabil Med, sv. 47, č. 3, pp. 367-373, 2011.

[16] J. Zeredo, K. Sasaki a K. Toda, „High-intensity laser for acupuncture-like stimulation,“ Lasers in medical science, sv. 22, č. 1, pp. 37-41, 2007.

[17] S. Wu a R. Maloney, „Low-level laser therapy: a possi- ble new light on wound healing,“ Podiatry Management, sv. 27,

pp. 105-110, 2008.

[1] A. Santamato, V. Solfrizzi, F. Panza, G. Tondi, V. Frisardi, B. G. Leggin, M. Ranieri a P. Fiore, „Short-term effects of high-intensity laser therapy versus ultrasound therapy in the treatment of people with subacromial impingement syndrome: a randomized clinical trial,“ Physical therapy, sv. 89, č. 7, pp. 643- 652, 2009.

[2] T. Ninomiya, Y. Miyamoto, T. Ito, A. Yamashita, M. Wakita a T. Nishisaka, „High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur,“ Journal of bone and mineral metabolism, sv. 21, č. 2, pp. 67-73, 2003.

[3] J. Marotti, F. F. Sperandio, E. R. Fregnani, A. C. C. Aranha, P. M. de Freitas a C. de Paula Eduardo, „High-intensity laser and photodynamic therapy as a treatment for recurrent herpes labialis,“ Photomedicine and Laser Surgery, sv. 28, č. 3, pp. 439- 444, 2010.

[4] K. A. Larkin, J. S. Martin, E. H. Zeanah, J. M. True, R.

W. Braith a P. A. Borsa, „Limb Blood Flow After Class 4 Laser Therapy,“ Journal of Athletic Training, sv. 47, č. 2, pp. 178-183, 2012.

[5] J. Kozarev a Z. Vizintin, „Novel laser therapy in treatment of onychomycosis,“ Journal of the Laser and Health Academy, sv. 1, pp. 1-8, 2010.

[6] L. G. Hochman, „Laser treatment of onychomycosis using a novel 0.65-millisecond pulsed Nd: YAG 1064-nm laser,“ Journal of Cosmetic and Laser Therapy, sv. 13, č. 1, pp. 2-5, 2011.

[7] A. Giuliani, M. Fernandez, M. Farinelli, L. Baratto, R. Capra, G. Rovetta, P. Monteforte, L. Giardino a L. Calza, „Very low level laser therapy attenuates edema and pain in experimental models,“ International journal of tissue reactions, sv. 26, pp. 29- 38, 2004.

[8] D. Fortuna, G. Rossi, T. W. Bilotta, A. Zati, V. Gazzotti,

A. Venturini, S. Pinna, C. Serra a L. Masotti, „High-intensity laser therapy during chronic degenerative tenosynovitis experimentally induced in broiler chickens,“ v Society of Photo-Optical Instru- mentation Engineers (SPIE) Conference Series, 2002.

[9] L. Brosseau, V. Robinson, G. Wells, R. Debie, A. Gam,

K. Harman, M. Morin, B. Shea a P. Tugwell, „Low level laser therapy (Classes I, II and III) for treating rheumatoid arthritis,“ Cochrane Database Syst Rev, sv. 4, 2005.