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Thiago De Marchi,1,2 Fabiano Frâncio,1,3 João Vitor Ferlito,3 Renata Weigert,3 Cristiane de Oliveira,3 Ana Paula Merlo,3 Délcio Luis Pandini,3 Bolivar Antônio Pasqual-Júnior,3 Daniela Giovanella,3 Shaiane Silva Tomazoni,4,5 Ernesto Cesar Leal-Junior2,4,5 1University Center of Bento Gonçalves (UNICNEC), Bento Gonçalves, Rio Grande do Sul, Brazil; 2Laboratory of Phototherapy and Innovative Technologies in Health (LaPIT), Post-graduate Program in Rehabilitation Sciences, Nove de Julho University, São Paulo, Brazil; 3Hospital Tacchini, Bento Gonçalves, Rio Grande do Sul, Brazil; 4Physiotherapy Research Group, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 5ELJ Consultancy, Scientific Consultants, São Paulo, BrazilCorrespondence: Shaiane Silva TomazoniPhysiotherapy Research Group, Department of Global Public Health and Primary Care, University of Bergen, Alrek helseklynge, blokk D, Årstadveien 17, Bergen, NO-5020, NorwayEmail shaiane.tomazoni@eljconsultancy.comPurpose: We aimed to investigate the effects of photobiomodulation therapy combined with static magnetic field (PBMT-sMF) on the length of intensive care unit (ICU) stay and mortality rate of severe COVID-19 patients requiring invasive mechanical ventilation and assess its role in preserving respiratory muscles and modulating inflammatory processes.Patients and Methods: We conducted a prospectively registered, triple-blinded, randomized, placebo-controlled trial of PBMT-sMF in severe COVID-19 ICU patients requiring invasive mechanical ventilation. Patients were randomly assigned to receive either PBMT-sMF or a placebo daily throughout their ICU stay. The primary outcome was length of ICU stay, defined by either discharge or death. The secondary outcomes were survival rate, diaphragm muscle function, and the changes in blood parameters, ventilatory parameters, and arterial blood gases.Results: Thirty patients were included and equally randomized into the two groups. There were no significant differences in the length of ICU stay (mean difference, MD = − 6.80; 95% CI = − 18.71 to 5.11) between the groups. Among the secondary outcomes, significant differences were observed in diaphragm thickness, fraction of inspired oxygen, partial pressure of oxygen/fraction of inspired oxygen ratio, C-reactive protein levels, lymphocyte count, and hemoglobin (p < 0.05).Conclusion: Among severe COVID-19 patients requiring invasive mechanical ventilation, the length of ICU stay was not significantly different between the PBMT-sMF and placebo groups. In contrast, PBMT-sMF was significantly associated with reduced diaphragm atrophy, improved ventilatory parameters and lymphocyte count, and decreased C-reactive protein levels and hemoglobin count.Trial Registration Number (Clinical Trials.gov): NCT04386694.Keywords: COVID-19, photobiomodulation, intensive care unit, respiratory muscles, ventilatory parameters, mechanical ventilation

Low-level laser therapy is a tool employed in the management of post-operative inflammation process and in the enhancement of reparative process. The aim of the study was to perform histological evaluation of dental and periodontal ligament of rats central upper-left incisor teeth re-implanted and irradiated with low-level laser (InGaAl, 685 nm, 50 J/cm(2)) 15, 30, and 60 days after re-implantation. Seventy-two male rats had the central upper left incisor removed and kept for 15 min on dry gauze before replantation. Laser was irradiated over the root surface and empty alveolus prior replantation and over surrounding mucosa after the re-implantation. After histological procedures, all slices were analyzed regarding external resorption area and histological aspects. We observed an increase of root resorption (p < 0.05) in the control group compared to the laser group at 15, 30, and 60 days. These results showed that the laser groups developed less root resorption areas than the control group in all experimental periods. Additionally, histological analysis revealed less inflammatory cells and necrotic areas in laser groups. [ABSTRACT FROM AUTHOR]

Arthritis of the knee is the most common type of joint inflammatory disorder and it is associated with pain and inflammation of the joint capsule. Few studies address the effects of the 810-nm laser in such conditions. Here we investigated the effects of low-level laser therapy (LLLT; infrared, 810-nm) in experimentally induced rat knee inflammation. Thirty male Wistar rats (230-250 g) were anesthetized and injected with carrageenan by an intra-articular route. After 6 and 12 h, all animals were killed by CO(2) inhalation and the articular cavity was washed for cellular and biochemical analysis. Articular tissue was carefully removed for real-time PCR analysis in order to evaluate COX-1 and COX-2 expression. LLLT was able to significantly inhibit the total number of leukocytes, as well as the myeloperoxidase activity with 1, 3, and 6 J (Joules) of energy. This result was corroborated by cell counting showing the reduction of polymorphonuclear cells at the inflammatory site. Vascular extravasation was significantly inhibited at the higher dose of energy of 10 J. Both COX-1 and 2 gene expression were significantly enhanced by laser irradiation while PGE(2) production was inhibited. Low-level laser therapy operating at 810 nm markedly reduced inflammatory signs of inflammation but increased COX-1 and 2 gene expression. Further studies are necessary to investigate the possible production of antiinflammatory mediators by COX enzymes induced by laser irradiation in knee inflammation. [ABSTRACT FROM AUTHOR]

Pain is the most common reason for physician consultations and the number one reason for missed work or school days is musculoskeletal pain. Pain management is utilized for easing the suffering and improving the Quality of Life of those living with chronic pain. Over the past several decades, physicians have become increasingly willing to prescribe opioids to manage pain. However, the opioid use can cause side effects as poor coordination, sedation, mood swings, depression, and anxiety combined with a dependence on the drugs. In the rehabilitation setting, patients benefit most when their health providers utilize a multimodal approach combining different types of therapies and when patients take on a significant role in optimal management of their own pain. The use of light as a therapeutic alternative form of medicine to manage pain and inflammation has been proposed to fill this void. Photobiomodulation therapy applied in the form of low-intensity Light Amplification by Stimulated Emission of Radiation (LASER) and light-emitting diode (LED) has been shown to reduce inflammation and swelling, promote healing, and reduce pain for an array of musculoskeletal conditions. There is evidence that photobiomodulation therapy reduces pain intensity in non-specific knee pain, osteoarthritis, pain post-total hip arthroplasty, fibromyalgia, temporomandibular diseases, neck pain, and low back pain. Therefore, the purpose of this paper was to present the up-to-dated evidence about the effects of low-intensity LASER and LED (photobiomodulation therapy) on pain control of the most common musculoskeletal conditions. We observed that the photobiomodulation therapy offers a non-invasive, safe, drug-free, and side-effect-free method for pain relief of both acute and chronic musculoskeletal conditions as well as fibromyalgia.

Photobiomodulation therapy (PBMT) has been indicated for enforcement on healing skin wounds. This study evaluated the effects of PBMT on the healing of skin wounds during the proliferation phase in rats with a hypoproteic diet. Rats were randomized to one of the following groups (n = 10 per group): (i) injured normoproteic (25% protein) not subjected to PBMT; (ii) injured normoproteic who received PBMT; (iii) injured hypoproteic (8% protein) not subjected to PBMT; and (iv) injured hypoproteic who received PBMT. Rats were submitted to skin wounds and then treated with PBMT (low-level laser therapy: 660 nm, 50 mW, 1.07 W/cm 2 , 0.028 cm 2 , 72 J/cm 2 , 2 J). Analyses were performed at 7 and 14 days of follow-up: semi-quantitative histopathologic analysis, collagen type I and III expressions, immunohistochemical marking for matrix metalloproteinases-3 (MMP-3) and (matrix metalloproteinases-9) MMP-9, and mechanical resistance test. There were significant differences between the normoproteic groups and their respective treated groups (p < 0.05), as well as to treated and untreated hypoproteic groups in histopathologic analysis semi-quantitatively and immunohistochemistry for MMP-3 and 9, in which PBMT was able to decrease immunostaining. Moreover, there was a decrease in collagen deposition with the statistical difference (p < 0.05) for both collagen types III and I. In conclusion, PBMT application was proved effective in the treatment of cutaneous wounds in rats submitted to a hypoproteic diet. These alterations were more salient in the proliferation stage with the reduction of metalloproteinases providing better mechanical resistance of the injured area in the remodeling phase with an intensification of type I collagen., (© 2020. Springer-Verlag London Ltd., part of Springer Nature.)

The post-myocardial infarction heart failure (HF) still carries a huge burden since current therapy is unsuccessful to abrogate poor prognosis. Thus, new approaches are needed, and photobiomodulation therapy (PBMt) may be a way. However, it is not known whether PBMt added to a standard HF therapy provides additional improvement in cardiac remodeling in infarcted rats. This study sought to determine the combined carvedilol-drug and PBMt with low-level laser therapy value in HF. Rats with large infarcts were treated for 30 days. The functional fitness was evaluated using a motorized treadmill. Echocardiography and hemodynamic measurements were used for functional evaluations of left ventricular (LV). ELISA, Western blot and biochemical assays were used to evaluate inflammation and oxidative stress in the myocardium. Carvedilol and PBMt had a similar action in normalizing pulmonary congestion and LV end-diastolic pressure, attenuating LV dilation, and improving LV systolic function. Moreover, the application of PBMt to carvedilol-treated rats inhibited myocardial hypertrophy and improved +dP/dt of LV. PBMt alone prevented inflammation with a superior effect than carvedilol. Carvedilol and PBMt normalized 4-hydroxynonenal (a lipoperoxidation marker) levels in the myocardium. However, importantly, the addition of PBMt to carvedilol attenuated oxidized protein content and triggered a high activity of the anti-oxidant catalase enzyme. In conclusion, these data show that the use of PBMt plus carvedilol therapy results in a significant additional improvement in HF in a rat model of myocardial infarction. These beneficial effects were observed to be due, at least in part, to decreased myocardial inflammation and oxidative stress.

Background: Photodynamic therapy (PDT) is an anticancer therapy that associates the photosensitizer (PS), oxygen and light to destroy cancer cells. Methylene blue (MB) is considered a second generation phenothiazine dye with excellent photochemical properties., Aim: To evaluate whether MB-mediated PDT can induce oxidative stress and inflammation, therefore, interfering tumor growth., Materials and Methods: The study was conducted on Wistar rats transplanted with Walker 256 carcinosarcoma (W256). The proinflammatory interleukins levels (IL-1β, IL-6, IL-10, TNF-α) were determined by ELISA, mRNA expression of COX-1, COX-2, iNOS and eNOS by RT-PCR, lipid peroxidation was measured by the TBARS method. Moreover, myeloperoxidase (MPO) activity in neutrophils was determined by MPO activity assay. All indices mentioned above were determined in tumor tissue. Kaplan - Meier and Gehan - Breslow - Wilcoxon tests were used for survival analysis., Results: We found that the treatment of W256 with 0.1% MB + 1 J/cm 2 provoked a significant increase in the interleukins levels (IL-1β, IL-6, IL-10, TNF-α), prostaglandin E2, the mRNA expression of COX-2, iNOS, lipid peroxidation and MPO activity in tumor tissue, which were statistically different (p < 0.05) compared to other experimental and control groups. The results of the estimation of survival curves show a greater probability of survival in 0.1% MB + 1 J/cm 2 (total energy dose =142.8 J/cm 2 ) treated group., Conclusion: Our results suggest that treatment of W256 with 0.1% MB + 1 J/cm 2 was able to promote cytotoxic effects in tumor tissue by the generation of reactive oxygen species causing inflammation and thus interfering in the tumor growth.

Objective : This systematic review and meta-analysis updated the effects of photobiomodulation therapy (PBMT) on pain, the Foot Function Index (FFI), and the effects on fascial thickness in adults with acute or chronic plantar fasciitis (PF). Methods : A systematic literature search was conducted in the PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases. Two researchers independently screened titles and abstracts of the retrieved studies for eligibility. A random-effects model was used for this meta-analysis. Subgroup meta-analyses were conducted to evaluate the influence of PBMT in pain and foot function under investigation and the study design on the overall weighted mean effect size. Results : From a total of 3865 studies, 7 randomized controlled trials were selected after final review and 4 were selected for meta-analysis. There was a significant difference between PBMT and control for Visual Analog Scale (Chi 2  = 29.30; p  < 0.00001) with an I 2 value of 90% in favor of PBMT versus the control. The overall effect of PBMT was statistically significant ( p  < 0.02) with PBMT favoring for thickness of the plantar fascia reduction. FFI between PBMT and control group [Chi 2 -83.46, df = 1 ( p  < 0.00001)]; I 2  = 99% in favor of the PBMT. Conclusions : This meta-analysis presents evidence that PBMT is an effective treatment modality to reduce pain and improvement of foot function in patients with chronic PF, however, a broad discrepancy was found in the PBMT dosimetry. The ideal treatment parameters for PF need to be elucidated.

This systematic review was performed to identify the role of photobiomodulation therapy in experimental models of third-degree burns used to induce oxidative stress. EMBASE, PubMed, and CINAHL databases were searched for studies published between January 2003 and January 2018 on the topics of photobiomodulation therapy and third-degree burns. Any study that assessed the effects of photobiomodulation therapy in animal models of third-degree burns was included in the analysis. A total of 17 studies were selected from 1182 original articles targeted on photobiomodulation therapy and third-degree burns. Two independent raters with a structured tool for rating the research quality critically assessed the articles. Although the small number of studies limits the conclusions, the current literature research indicates that photobiomodulation therapy can be an effective short-term approach to accelerate the healing process of third-degree burns, to increase and modulate the inflammatory process, to accelerate the proliferation of fibroblasts, and to enhance the quality of the collagen network. However, differences still exist in the terminology used to describe the parameters and the dose of photobiomodulation therapy.

This study aimed to determine whether photobiomodulation therapy (PBMT) in diabetic rats subjected to high-intensity exercise interferes with the expression of the oxidative stress marker in the gastrocnemius muscle. Twenty-four male Wistar rats were included in this study comprising 16 diabetic and eight control rats. The animals were allocated into three groups-control, diabetic fatigue, and diabetic PBMT fatigue groups. Diabetes was induced via the intraperitoneal administration of streptozotocin (50 mg/kg). We subsequently assessed blood lactate levels and PBMT. The animals of the diabetic fatigue group PBMT were irradiated before the beginning of the exercises, with dose of 4 J and 808 nm, were submitted to treadmill running with speed and gradual slope until exhaustion, as observed by the maximum volume of oxygen and lactate level. The animals were euthanized and muscle tissue was removed for analysis of SOD markers, including catalase (CAT), glutathione peroxidase (GPx), and 2-thiobarbituric acid (TBARS) reactive substances. CAT, SOD, and GPx activities were significantly higher in the diabetic PBMT fatigue group (p < 0.05) than in the diabetic fatigue group. Outcomes for the diabetic PBMT fatigue group were similar to those of the control group (p > 0.05), while their antioxidant enzymes were significantly higher than those of the diabetic fatigue group. PBMT mitigated the TBARS concentration (p > 0.05). PBMT may reduce oxidative stress and be an alternative method of maintaining physical fitness when subjects are unable to perform exercise. However, this finding requires further testing in clinical studies.

This study aimed to determine whether photobiomodulation therapy (PBMT) could improve the bioavailability and chondroprotective benefits of mesenchymal stem cells injected into the knees of rats used as an experimental model of osteoarthritis (OA) as well as reduce the expression of matrix metalloproteinases (MMPs) and degradation of type II collagen (COL2-1) in the cartilage. Adipose-derived stem/stromal cells (ADSCs) were collected from three male Fischer 344 rats and characterized by flow cytometry. Fifty female Fischer 344 rats were distributed into five groups of 10 animals each. These groups were as follows: control, OA, OA PBMT, OA ADSC, and OA ADSC PBMT. OA was induced in the animals using a 4% papain solution. Animals from the OA ADSC and OA ADSC PBMT groups received an intra-articular injection of 10 × 10 6 ADSCs and were treated with PBMT by irradiation (wavelength: 808 nm, power: 50 mW, energy: 42 J, energy density: 71.2 J/cm 2 , spot size: 0.028). Euthanasia was performed 7 days after the first treatment. The use of PBMT alone and the injection of ADSCs resulted in downregulation of pro-inflammatory cytokines and MPs in cartilage compared to the OA group. PBMT and ADSCs caused upregulation of tissue inhibitors of MPs 1 and 2 and mRNA and protein expression of COL2-1 in cartilage compared to the OA group. The intra-articular injection of ADSCs and PBMT prevented joint degeneration resulting from COL2-1 degradation and modulated inflammation by downregulating cytokines and MMPs in the OA group.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic and systemic inflammation, which leads to the destruction of the cartilage and bone and affects tissues in multiple joints. Oxidative stress has been implicated with regards to involvement in various disease conditions, such as diabetes mellitus and neurodegenerative, respiratory, cardiovascular, and RA diseases. In vivo experimental studies using photobiomodulation therapy (PBMT) have shown positive effects in reducing lipid peroxidation and in increasing antioxidant activity. The regular practice of physical exercise has also been reported to be a beneficial treatment capable of reducing oxidative damage. Thus, the aim of this study was to analyze the effects of photobiomodulation therapy at 2- and 4-J doses associated with physical exercise on oxidative stress in an experimental model of RA in protein expression involving superoxide dismutase (SOD), glutathione peroxidase (GPX), and/or catalase (CAT) on thiobarbituric acid reactive substances (TBARS). In this study, 24 male Wistar rats divided into four groups were submitted to an RA model (i.e., collagen-induced arthritis, CIA), with the first immunization performed at the base of the tail on days 0 and 7 were included. After 28 days, a third intraarticular dose was administered in both knees of the animals. After the last induction, PBMT was started immediately, transcutaneously at two points (i.e., the medial and lateral), with a total of 15 applications. Treadmill exercise was also started the day after the last induction, and lasted for 5 weeks. With respect to results, we obtained the decreases in the lipid peroxidation and the increases of the antioxidant activities of SOD, GPX and CAT, with physical exercise associated to PBMT in doses of 2 and 4 J. In conclusion, physical exercise associated with PBMT decreases lipid peroxidation and increases antioxidant activity.

This study aimed to determine the effectiveness of photobiomodulation therapy (PBMT) and cryotherapy, in isolated and combined forms, as muscle recovery techniques after muscle fatigue-inducing protocol. Forty volunteers were randomly divided into five groups: a placebo group (PG); a PBMT group (PBMT); a cryotherapy group (CG); a cryotherapy-PBMT group (CPG); and a PBMT-cryotherapy group (PCG). All subjects performed four sessions at 24-h intervals, during which they submitted to isometric assessment (MVC) and blood collection in the pre-exercise period, and 5 and 60 min post-exercise, while the muscle fatigue induction protocol occurred after the pre-exercise collections. In the remaining sessions performed 24, 48, and 72 h later, only blood collections and MVCs were performed. A single treatment with PBMT and/or cryotherapy was applied after only 2 min of completing the post-5-min MVC test at the first session. In the intragroup comparison, it was found that exercise led to a significant decrease (p < 0.05) in the production of MVC in all groups. Comparing the results of MVCs between groups, we observed significant increases in the MVC capacity of the PBMT, CPG, and PCG volunteers in comparison with both PG and CG (p < 0.05). We observed a significant decrease in the concentrations of the biochemical markers of oxidative damage (TBARS and PC) in all groups and muscle damage (creatine kinase-CK) in the PBMT, PCG, and CPG compared with the PG (p < 0.01). The clinical impact of these findings is clear because they demonstrate that the use of phototherapy is more effective than the use of cryotherapy for muscle recovery, additionally cryotherapy decreases PBMT efficacy.

Osteoarthritis (OA) triggers increased levels of inflammatory markers, including prostaglandin (PG) E 2 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 PGE 2 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 PGE 2 (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.

The objective of this study was to evaluate the effects of photobiomodulation therapy (PBMT) on inflammatory indicators, i.e., inflammatory mediators (TNF-α and CINC-1), and pain characterized by hyperalgesia and B1 and B2 receptor activation at 6, 24, and 48 h after papain-induced osteoarthritis (OA) in rats. Fifty-four rats were subjected to hyperalgesia evaluations and then divided randomly into three groups-a control group and two groups OA and OA PBMT group by using laser parameters at wavelength (808 nm), output power (50 mW), energy per point (4 Joules), power density (1.78 W/cm 2 ), laser beam (0.028 cm 2 ), and energy density (144 J/cm 2 )-the induction of osteoarthritis was then performed with 20-μl injections of a 4 % papain solution dissolved in 10 μl of saline solution, to which 10 μl of cysteine solution (0.03 M). The statistical analysis was performed using two-way ANOVA with Bonferroni's post hoc test for comparisons between the 6, 24, and 48 h and team points within each group, and between the control, injury, and PBMT groups, and p < 0.05 was considered to indicate a significant difference. The hyperalgesia was evaluated at 6, 24, and 48 h after the injury. PBMT at a wavelength of 808 nm and doses of 4 J, administered afterward, promotes increase at the threshold of pressure stimulus at 6, 24, and 48 h after application and promote cytokine attenuation levels (TNF and CINC-1) and bradykinin receptor (B1 and B2) along the experimental period. We conclude that photobiomodulation therapy was able to promote the reduction of proinflammatory cytokines such as TNF-α and CINC-1, to reduce the gene and protein expression of the bradykinin receptor (B1 and B2), as well as increasing the stimulus response threshold of pressure in an experimental model of acute osteoarthritis.

This systematic review was performed to identify the role of photobiomodulation therapy on experimental muscle injury models linked to induce oxidative stress. EMBASE, PubMed, and CINAHL were searched for studies published from January 2006 to January 2016 in the areas of laser and oxidative stress. Any animal model using photobiomodulation therapy to modulate oxidative stress was included in analysis. Eight studies were selected from 68 original articles targeted on laser irradiation and oxidative stress. Articles were critically assessed by two independent raters with a structured tool for rating the research quality. Although the small number of studies limits conclusions, the current literature indicates that photobiomodulation therapy can be an effective short-term approach to reduce oxidative stress markers (e.g., thiobarbituric acid-reactive) and to increase antioxidant substances (e.g., catalase, glutathione peroxidase, and superoxide dismutase). However, there is a nonuniformity in the terminology used to describe the parameters and dose for low-level laser treatment.

Cryotherapy for post-exercise recovery remains widely used despite the lack of quality evidence. Photobiomodulation therapy (PBMT) studies (with both low-level laser therapy and light-emitting diode therapy) have demonstrated positive scientific evidence to suggest its use. The study aims to evaluate PBMT and cryotherapy as a single or combined treatment on skeletal muscle recovery after eccentric contractions of knee extensors. Fifty healthy male volunteers were recruited and randomized into five groups (PBMT, cryotherapy, cryotherapy + PBMT, PMBT + cryotherapy, or placebo) for a randomized, double-blinded, placebo-controlled trial that evaluated exercise performance (maximum voluntary contraction (MVC)), delayed onset muscle soreness (DOMS), and muscle damage (creatine kinase (CK)). Assessments were performed at baseline; immediately after; and at 1, 24, 48, 72, and 96 h. Comparator treatments was performed 3 min after exercise and repeated at 24, 48, and 72 h. PBMT was applied employing a cordless, portable GameDay ™ device (combination of 905 nm super-pulsed laser and 875- and 640-nm light-emitting diodes (LEDs); manufactured by Multi Radiance Medical ™ , Solon - OH, USA), and cryotherapy by flexible rubber ice packs. PBMT alone was optimal for post-exercise recovery with improved MVC, decreased DOMS, and CK activity (p < 0.05) from 24 to 96 h compared to placebo, cryotherapy, and cryotherapy + PBMT. In the PBMT + cryotherapy group, the effect of PBMT was decreased (p > 0.05) but demonstrated significant improvement in MVC, decreased DOMS, and CK activity (p < 0.05). Cryotherapy as single treatment and cryotherapy + PBMT were similar to placebo (p > 0.05). We conclude that PBMT used as single treatment is the best modality for enhancement of post-exercise restitution, leading to complete recovery to baseline levels from 24 h after high-intensity eccentric contractions.

This study investigates the effect of photobiomodulation therapy (PBMT) on collagen type I and III, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF) in experimentally induced tendinopathy in female aged rats. Tendinopathy was induced by the Achilles tendoncollagenase peritendinous. Forty-two Wistar rats (Norvegicus albinus) were used; groups consisted of 36 aged animals (18 months old; mean body weight, 517.7 ± 27.54 g) and 6 adult animals (12 weeks old; mean body weight, 266± 19.30 g). The animals were divided into three groups: control, aged tendinopathy, and aged tendinopathy PBMT; the aged groups were subdivided based on time to euthanasia: 7, 14, and 21 days. PBMT involved a gallium-arsenide-aluminum laser (Theralaser, DMC®) with active medium operating at wavelength 830 ± 10 nm, 50 mW power, 0.028 cm 2 laser beam, 107 J/cm 2 energy density, 1.8 W/cm 2 power density, and an energy of 3 J per point. The laser was applied by direct contact with the left Achilles tendon during 60 s per point at a frequency of three times per week, until the euthanasia date (7, 14, and 21 days). VEGF, MMP-3, and MMP-9 were analyzed by immunohistochemistry, and collagen type I and III by Sirius red. PBMT increased the deposition of collagen type I and III in a gradual manner, with significant differences relative to the group aged tendonitis (p < 0.001), and in relation to VEGF (p < 0.001); decreased expression of MMP-3 and 9 were observed in group aged tendinopathy (p < 0.001). PBMT, therefore, increased the production of collagen type I and III, downregulated the expression of MMP-3 and MMP-9, and upregulated that of VEGF, with age and age-induced hormonal deficiency.

Pinto, HD, Vanin, AA, Miranda, EF, Tomazoni, SS, Johnson, DS, Albuquerque-Pontes, GM, de Oliveira Aleixo Junior, I, Grandinetti, VdS, Casalechi, HL, de Tarso Camillo de Carvalho, P, and Pinto Leal Junior. Photobiomodulation therapy 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 30(12): 3329-3338, 2016-Although growing evidence supports the use of photobiomodulation therapy (PBMT) for performance and recovery enhancement, there have only been laboratory-controlled studies. Therefore, the aim of this study was to analyze the effects of PBMT in performance and recovery of high-level rugby players during an anaerobic field test. Twelve male high-level rugby athletes were recruited in this randomized, crossover, double-blinded, placebo-controlled trial. No interventions were performed before the Bangsbo sprint test (BST) at familiarization phase (week 1); at weeks 2 and 3, pre-exercise PBMT or placebo were randomly applied to each athlete. Photobiomodulation therapy irradiation was performed at 17 sites of each lower limb, employing a cluster with 12 diodes (4 laser diodes of 905 nm, 4 light emitting diodes [LEDs] of 875 nm, and 4 LEDs of 640 nm, 30 J per site, manufactured by Multi Radiance Medical). Average time of sprints, best time of sprints, and fatigue index were obtained from BST. Blood lactate levels were assessed at baseline, and at 3, 10, 30, and 60 minutes after BST. Athletes' perceived fatigue was also assessed through a questionnaire. Photobiomodulation therapy significantly (p ≤ 0.05) improved the average time of sprints and fatigue index in BST. Photobiomodulation therapy significantly decreased percentage of change in blood lactate levels (p ≤ 0.05) and perceived fatigue (p ≤ 0.05). Pre-exercise PBMT with the combination of super-pulsed laser (low-level laser), red LEDs, and infrared LEDs can enhance performance and accelerate recovery of high-level rugby players in field test. This opens a new avenue for wide use of PBMT in real clinical practice in sports settings.

Background: The temporomandibular joint (TMJ) is a structure of the craniofacial complex affected by neurological diseases. Orthopedic and musculoskeletal changes can also cause temporomandibular disorders (TMD) and pain. Low-level laser (LLL) therapy has been studied in the treatment of temporomandibular jaw (TMJ) dysfunction, and controversial results were obtained., Objective: The objective of this work was comparing the physiotherapeutic and drug protocol (PDP) to LLL therapy in the treatment of pain associated with TMD., Methods: A sample of 60 female patients, 20-50 years of age, TMD triggering agents (stress, parafunctional habits) controlled, was randomly divided into three groups, group 1 (G1)-LLL (780 nm laser, dose of 35.0 J/cm 2 , for 20 sec, thrice a week, for 4 weeks); group 2 (G2)-PDP (hot packs thrice a day, morning, afternoon, and evening, for 15 min, exercise of opening and closing the mouth, twice a day, myorelaxing and anti-inflammatory drug administration); and group 3 (G3)-Placebo (450 nm halogen lamp, Max LD Gnatus, light curing unit)., Results: Patients were evaluated every return appointment for the presence (P) or absence (A) of pain for 4 weeks and results were statistically analyzed. First week: 60% of G1, 100% G2, and 70% of G3-related pain. Second week: 55% of G1, 15% of G2, and 100% of G3-related pain. Third week: 10% of G1, 15% of G2, and 85% of G3-related pain. Last week: 0% of G1, 0% of G2, and 100% of G3-related pain., Conclusions: Based on obtained data, we concluded that, compared to PDP, LLL treatment is effective to control pain associated with TMD.

The effects of phototherapy (or photobiomodulation therapy) with low-level laser therapy (LLLT) and/or light-emitting diodes (LEDs) on human performance improvement have been widely studied. Few studies have examined its effect on muscular training and no studies have explored the necessary moment of phototherapy irradiations (i.e., before and/or after training sessions). The aim of this study was to determine the optimal moment to apply phototherapy irradiation when used in association with strength training. Forty-eight male volunteers (age between 18 to 35 years old) completed all procedures in this study. Volunteers performed the strength training protocol where either a phototherapy and/or placebo before and/or after each training session was performed using cluster probes with four laser diodes of 905 nm, four LEDs of 875 nm, and four LEDs of 640 nm-manufactured by Multi Radiance Medical™. The training protocol duration was 12 weeks with assessments of peak torque reached in maximum voluntary contraction test (MVC), load in 1-repetition maximum test (1-RM) and thigh circumference (perimetry) at larger cross-sectional area (CSA) at baseline, 4 weeks, 8 weeks, and 12 weeks. Volunteers from group treated with phototherapy before and placebo after training sessions showed significant (p < 0.05) changes in MVC and 1-RM tests for both exercises (leg extension and leg press) when compared to other groups. With an apparent lack of side effects and safety due to no thermal damage to the tissue, we conclude that the application of phototherapy yields enhanced strength gains when it is applied before exercise. The application may have additional beneficial value in post-injury rehabilitation where strength improvements are needed.

Osteoarthritis (OA) is a chronic inflammatory disease and is characterized as a degenerative process. This study aimed to evaluate and compare the effects of a topical nonsteroidal anti-inflammatory drug (NSAID), physical activity, and photobiomodulation therapy (PBMT) applied alone and/or in combination between them in an experimental model of knee OA. OA was induced by injection of papain in the knees of rats. After 21 days, the animals started to be treated with the above treatment. Histological analysis shows that the experimental model of OA induction causes morphological changes consistent with the disease, and among treatments, the PBMT is the most effective for reducing these changes. Moreover, the results demonstrate that PBMT and NSAID reduce the total number of cells in the inflammatory infiltrate (p<0.05) and PBMT was the most effective for reducing the activity of myeloperoxidase (p<0.05). Finally, we observed that both NSAID and PBMT were effective for reducing the gene expression of MMP-3 (p<0.05), but in relation to the gene expression of MMP-13, PBMT was the most effective treatment (p<0.05). The results of this study indicate that PBMT is the most effective therapy in stopping disease progression, and improving inflammatory conditions observed in OA.

Aim: This study aimed to evaluate the medium-term effects of low-level laser therapy (LLLT or photobiomodulation) in postexercise skeletal muscle recovery and performance enhancement and to identify the optimal dose of 810 nm LLLT., Materials and Methods: A randomized, double-blind, placebo-controlled trial was performed, with voluntary participation of 28 high-level soccer athletes. We analyzed maximum voluntary contraction (MVC), delayed onset muscle soreness (DOMS), creatine kinase (CK) activity, and interleukin-6 (IL-6) expression. The assessments were performed before exercise protocols, after 1 min, and 1, 24, 48, 72, and 96 h after the end of eccentric exercise protocol used to induce fatigue. LLLT was applied before eccentric exercise protocol with a cluster with five diodes, and dose of 10, 30, or 50 J (200 mW and 810 nm) in six sites of quadriceps., Results: LLLT increased (p < 0.05) MVC from immediately after exercise to 24 h with 50 J dose, and from 24 to 96 h with 10 J dose. Both 10 J then 50 J dose decreased (p < 0.05) CK and IL-6 with better results in favor of 50 J dose. However, LLLT had no effect in decreasing DOMS. No differences (p > 0.05) were found for 30 J dose in any of the outcomes measured., Conclusions: Pre-exercise LLLT, mainly with 50 J dose, significantly increases performance and improves biochemical markers related to skeletal muscle damage and inflammation.

The aim of the present study was to determine whether low-level laser therapy (LLLT) in conjunction with aerobic training interferes with oxidative stress, thereby influencing the performance of old rats participating in swimming. Thirty Wistar rats (Norvegicus albinus) (24 aged and six young) were tested. The older animals were randomly divided into aged-control, aged-exercise, aged-LLLT, aged-LLLT/exercise, and young-control. Aerobic capacity (VO2max(0.75)) was analyzed before and after the training period. The exercise groups were trained for 6 weeks, and the LLLT was applied at 808 nm and 4 J energy. The rats were euthanized, and muscle tissue was collected to analyze the index of lipid peroxidation thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. VO2 (0.75)max values in the aged-LLLT/exercise group were significantly higher from those in the baseline older group (p <0.01) and the LLLT and exercise group (p <0.05). The results indicate that the activities of CAT, SOD, and GPx were higher and statistically significant (p <0.05) in the LLLT/exercise group than those in the LLLT and exercise groups. Young animals presented lesser and statistically significant activities of antioxidant enzymes compared to the aged group. The LLLT/exercise group and the LLLT and exercise group could also mitigate the concentration of TBARS (p > 0.05). Laser therapy in conjunction with aerobic training may reduce oxidative stress, as well as increase VO2 (0.75)max, indicating that an aerobic exercise such as swimming increases speed and improves performance in aged animals treated with LLLT.

Context: Skeletal muscle fatigue and exercise performance are novel areas of research and clinical application in the photobiomodulation field, and positive outcomes have been reported in several studies; however, the optimal measures have not been fully established., Objective: To assess the acute effect of photobiomodulation therapy (PBMT) combining superpulsed lasers (low-level laser therapy) and light-emitting diodes (LEDs) on muscle performance during a progressive cardiopulmonary treadmill exercise test., Design: Crossover study., Setting: Laboratory., Patients or Other Participants: Twenty untrained male volunteers (age = 26.0 ± 6.0 years, height = 175.0 ± 10.0 cm, mass = 74.8 ± 10.9 kg)., Intervention(s): Participants received PBMT with either combined superpulsed lasers and LED (active PBMT) or placebo at session 1 and the other treatment at session 2. All participants completed a cardiopulmonary test on a treadmill after each treatment. For active PBMT, we performed the irradiation at 17 sites on each lower limb (9 on the quadriceps, 6 on the hamstrings, and 2 on the gastrocnemius muscles), using a cluster with 12 diodes (four 905-nm superpulsed laser diodes with an average power of 0.3125 mW, peak power of 12.5 W for each diode, and frequency of 250 Hz; four 875-nm infrared LED diodes with an average power of 17.5 mW; and four 640-nm red LED diodes with an average power of 15 mW) and delivering a dose of 30 J per site., Main Outcome Measure(s): Distance covered, time until exhaustion, pulmonary ventilation, and dyspnea score., Results: The distance covered (1.96 ± 0.30 versus 1.84 ± 0.40 km, t19 = 2.119, P < .001) and time until exhaustion on the cardiopulmonary test (780.2 ± 91.0 versus 742.1 ± 94.0 seconds, t19 = 3.028, P < .001) was greater after active PBMT than after placebo. Pulmonary ventilation was greater (76.4 ± 21.9 versus 74.3 ± 19.8 L/min, t19 = 0.180, P = .004) and the score for dyspnea was lower (3.0 [interquartile range = 0.5-9.0] versus 4.0 [0.0-9.0], U = 184.000, P < .001) after active PBMT than after placebo., Conclusions: The combination of lasers and LEDs increased the time, distance, and pulmonary ventilation and decreased the score of dyspnea during a cardiopulmonary test.

The aim of this experimental study was to investigate the effects of low-intensity light-emitting diode (LED) phototherapy on the inflammatory process in the calcaneal tendon of ovariectomized rats (OVX) through the involvement of the inflammatory mediators interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Thirty-five female Wistar rats were divided into 4 groups: 3 groups of OVX rats totaling 30 rats (untreated OVX rats [OVX injury group], treated OVX rats [OVX LED group], and control OVX rats; subgroups existed based on the sampling times, which were 3, 7, and 14 days) and 1 group of non-OVX rats (not OVX; n = 5). Tendon injury was induced by trauma using a 208-g mass placed at 20 cm from the right tendon of each animal with energy of 0.70 J. The animals were treated 12 h after tendonitis with LED therapy and every 48 h thereafter until euthanasia (at 3, 7, or 14 days). The tendons were dissected and stored in liquid nitrogen at -196 °C, thawed only at the time of immunoenzymatic testing (ELISA). Groups treated with LED showed a decrease in the number of pro-inflammatory cells, IL-6, and TNF-α (p <0.05), and an increase in IL-10 (p < 0.05) when compared to the not OVX group (p < 0.05). It was concluded that low-intensity LED treatment using the parameters and wavelength of 945 nm in the time periods studied reduced the release of IL-6 and TNF-α and increased the release of IL-10, thereby improving the inflammatory response in OVX rats.

Objective: The objective of this study was to evaluate the effect of laser irradiation on dog bone marrow stem cells., Background Data: Low doses of low-level red laser positively affect the viability of mesenchymal stem cells, and also increase proliferation., Methods: Low-level laser (wavelength, 660 nm; power output, 50 mW), was applied to dog bone marrow stem cell cultures (DBMSC). The energy densities delivered varied from 1 to 12J/cm(2). The effect of the laser irradiation was evaluated on cell proliferation measured with the MTT colorimetric test, cell cycle phase, and on lipidic peroxidation (free radical production)., Results: The results indicate that laser irradiation to DBMSC did not change the morphology of the cells, but significantly increased their viability and the number of cells at the G2/M phase with 6, 10, and 12 J/cm(2). On the other hand, malonaldehyde production was significantly enhanced with 8 J/cm(2)., Conclusions: The parameters used to irradiate DBMSC increased significantly proliferation without producing high levels of reactive oxygen species (ROS).

Tendinopathy is a common disease with a variety of treatments and therapies. Laser therapy appears as an alternative treatment. Here, we investigate the effects of laser irradiation in an experimental model of tendinitis induced by collagenase injection on rats' Achilles tendon, verifying its action in important inflammatory markers. Male Wistar rats were used and divided into five groups: control saline (C), non-treated tendinitis (NT) and tendinitis treated with sodium diclofenac (D) or laser (1 J) and (3 J). The tendinitis was induced by collagenase (100 μg/tendon) on the Achilles tendon, which was removed for further analyses. The gene expression for COX-2; TNF-α; IL-6; and IL-10 (RT-PCR) was measured. The laser irradiation (660 nm, 100 mW, 3 J) used in the treatment of the tendinitis induced by collagenase in Achilles tendon in rats was effective in the reduction of important pro-inflammatory markers such as IL-6 and TNF-α, becoming a promising tool for the treatment of tendon diseases.

This study was designed to determine if the levels of oxidative stress markers are influenced by low-level laser therapy (LLLT) in mdx mice subjected to high-intensity exercise training on an electric treadmill. We used 21 C57BL/10ScSn-Dmdmdx/J mice and 7 C57BL/10ScSn mice, all aged 4 weeks. The mice were divided into four groups: a positive control group of normal, wild-type mice (WT); a negative control group of untreated mdx mice; a group of mdx mice that underwent forced high-intensity exercise on a treadmill (mdx fatigue); and another group of mdx mice with the same characteristics that were treated with LLLT at a single point on the gastrocnemius muscle of the hind paw and underwent forced high-intensity exercise on a treadmill. The mdx mice treated with LLLT showed significantly lower levels of creatine kinase (CK) and oxidative stress than mdx mice that underwent forced high-intensity exercise on a treadmill. The activities of the antioxidant enzyme superoxide dismutase (SOD) were higher in control mdx mice than in WT mice. LLLT also significantly reduced the level of this marker. LLLT had a beneficial effect also on the skeletal muscle performance of mdx mice. However, the single application of LLLT and the dose parameters used in this study were not able to change the morphology of a dystrophic muscle.

From the very first reports describing the method of action of phototherapy, the effects have been considered to be the result of photochemical and photophysical interactions between the absorbed photons and tissue and not related to secondary changes in tissue or skin temperature. However, thermal effects have been recently reported in dark pigmented skin when irradiated with single wavelengths of 810 and 904 nm of low-level laser therapy (LLLT) devices even with doses that do not exceed those recommended by the World Association of Laser Therapy (WALT). The aim of this study was to evaluate the thermal impact during the concurrent use of pulsed red and infrared LEDs and super-pulsed lasers when applied to light, medium, and dark pigmented human skin with doses typically seen in clinical practice. The study evaluated the skin temperature of 42 healthy volunteers (males and females 18 years or older, who presented different pigmentations, stratified according to Von Luschan's chromatic scale) via the use of a thermographic camera. Active irradiation was performed with using the multi-diode phototherapy cluster containing four 905-nm super-pulsed laser diodes (frequency set to 250 Hz), four 875-nm infrared-emitting diodes, and four 640-nm LEDs (manufactured by Multi Radiance Medical™, Solon, OH, USA). Each of the four doses were tested on each subject: placebo, 0 J (60 s); 10 J (76 s); 30 J (228 s); and 50 J (380 s). Data were collected during the last 5 s of each dose of irradiation and continued for 1 min after the end of each irradiation. No significant skin temperature increases were observed among the different skin color groups (p > 0.05), age groups (p > 0.05), or gender groups (p > 0.05). Our results indicate that the concurrent use of super-pulsed lasers and pulsed red and infrared LEDs can be utilized in patients with all types of skin pigmentation without concern over safety or excessive tissue heating. Additionally, the doses and device utilized in present study have demonstrated positive outcomes in prior clinical trials. Therefore, it can be concluded that the effects seen by the concurrent use of multiple wavelengths and light sources were the result of desirable photobiomodulation effect and not related to thermal influence.

Background: Fibromyalgia (FM) is a syndrome most prevalent in women, in whom it is characterized mainly by chronic pain. An important issue is that many patients with FM are reported to have temporomandibular dysfunction (TMD), and the coexistence of these pathologies generates a clinical outcome of high complexity. The literature is unclear regarding an effective therapy for reducing pain in patients with both comorbidities. Exercise training and phototherapy (low-level laser therapy with light-emitting diode) are two of the approaches used to treat pain. Thus, the aim of this study is to assess the potential role of exercise training plus phototherapy in reducing chronic pain in women with FM and TMD. A further aim is to determine whether the interventions can improve quality of life and modulate endogenous serotonin., Methods/design: A randomized controlled clinical trial will be conducted. It will involve 60 women ≥ 35 years of age with a diagnosis of FM and TMD. After recruitment, patients will be randomly allocated to one of four groups: a control group (no intervention), a group that will receive a phototherapy intervention (PHO), a group that will be prescribed muscle-stretching, aerobic, and facial exercises (EXT), or a group that will receive phototherapy plus exercise interventions (PHO + EXT). The trial will last 10 weeks, and the following outcomes will be evaluated on two separate occasions (baseline and within 24 h after the last day of the protocol). Pain intensity will be analyzed using a visual analogue scale and the McGill Pain Questionnaire, and pain thresholds will be punctuated using a digital algometer. FM symptoms will be assessed using the Fibromyalgia Impact Questionnaire, and quality of life will be determined with the 36-item Short Form Health Survey. Serotonin levels will be evaluated in salivary samples using a competitive enzyme-linked immunosorbent assay., Discussion: This is the first randomized controlled trial in which the role of phototherapy, exercise training, and a combination of these interventions will be evaluated for chronic pain in patients with FM and TMD. The results will offer valuable clinical evidence for objective assessment of the potential benefits and risks of procedures., Trial Registration: ClinicalTrials.gov Identifier: NCT02279225. Registered 27 October 2014.

The aim of the present study was to determine whether low-level laser therapy (LLLT), when used in conjunction with aerobic training, interferes with the expression of inflammatory markers IL-6 and TNF-α, thereby influencing the performance of old rats participating in swimming. A total of 30 Wistar rats (Rattus norvegicus albinus) were used for this study: 24 aged rats, and 6 young rats. The older animals were randomly divided into four groups designated as follows: aged-control, aged-exercise, aged-LLLT, aged-LLLT/exercise group, and young-control animals. Aerobic capacity (VO2max) was analyzed before and after training period. The aged-exercise and aged-LLLT/exercise groups were trained for 6 weeks. LLLT laser was applied before each training session with 808 nm and 4 J of energy to the indicated groups throughout training. The rats were euthanized, and muscle tissue and serum were collected for muscle cross-sectional area and IL-6 and TNF-α protein analysis. In VO2 showed statistical difference between young- and aged-control groups (used as baseline) (p < 0.05). The same difference can be observed in the young control group compared with all intervention groups (exercise, LLLT and LLLT + exercise). In comparison with the aged-control group, a difference was observed only for comparison with the exercise group (p < 0.05), and exercise associated with LLLT group (p < 0.001). Levels of IL-6 and TNF-α for the aged-exercise and the aged-LLLT/exercise groups were significantly decreased compared to the aged-control group (p < 0.05). Analysis of the transverse section of the gastrocnemius muscle showed a significant difference between the aged-exercise and aged-LLLT/exercise groups (p < 0.001). These results suggest that laser therapy in conjunction with aerobic training may provide a therapeutic approach for reducing the inflammatory markers (IL-6 and TNF-α), however, LLLT without exercise was not able to improve physical performance of aged rats.

Background and Objective: Freezing changes sperm integrity remarkably. Cryopreservation involves cooling, freezing, and thawing and all these contribute to structural damage in sperm, resulting in reduced fertility potential. Low-level laser irradiation (LLLI) could increase energy supply to the cell and cause reactive oxygen species reduction (ROS), contributing to the restoration of oxygen consumption and adenosine triphosphate synthesis (ATP) in the mitochondria. Our goal was to analyze the effects of low-level laser irradiation on sperm motility and integrity of the plasma membrane and acrosome in cryopreserved bovine sperm., Study Design/materials and Methods: We analyzed 09 samples of bull semen (Bos taurus indicus), divided into three groups: a control group without laser irradiation, a 4J group subjected to a laser irradiation dose of 4 joules, and a 6J group subjected to dose of 6 joules. Samples were divided for the analysis of cell viability and acrosomal membrane integrity using flow cytometry; another portion was used for motion analysis. Irradiation was performed in petri dishes of 30 mm containing 3 ml of semen by an aluminum gallium indium phosphide laser diode with a wavelength of 660 nm, 30 mW power, and energy of 4 and 6 joules for 80 and 120 seconds respectively. Subsequently, the irradiated and control semen samples were subjected to cryopreservation and analyzed by flow cytometry (7AAD and FITC-PSA) using the ISAS--Integrated Semen Analysis System., Results: Flow cytometry showed an increase in the percentage of live sperm cells and acrosome integrity in relation to control cells when subjected to irradiation of low-power laser in two different doses of 4 and 6 joules (p < 0.05). In the analysis of straightness, percentage of cell movement, and motility, a dose of 4 joules was more effective (p < 0.05)., Conclusion: We conclude that LLLI may exert beneficial effects in the preservation of live sperm. A dose of 4 joules prior to cryopreservation was more effective than a dose of 6 joules in preserving sperm motility.

Recent studies have explored if phototherapy with low-level laser therapy (LLLT) or narrow-band light-emitting diode therapy (LEDT) can modulate activity-induced skeletal muscle fatigue or subsequently protect against muscle injury. We performed a systematic review with meta-analysis to investigate the effects of phototherapy applied before, during and after exercises. A literature search was performed in Pubmed/Medline database for randomized controlled trials (RCTs) published from 2000 through 2012. Trial quality was assessed with the ten-item PEDro scale. Main outcome measures were selected as: number of repetitions and time until exhaustion for muscle performance, and creatine kinase (CK) activity to evaluate risk for exercise-induced muscle damage. The literature search resulted in 16 RCTs, and three articles were excluded due to poor quality assessment scores. From 13 RCTs with acceptable methodological quality (≥6 of 10 items), 12 RCTs irradiated phototherapy before exercise, and 10 RCTs reported significant improvement for the main outcome measures related to performance. The time until exhaustion increased significantly compared to placebo by 4.12 s (95% CI 1.21-7.02, p < 0.005) and the number of repetitions increased by 5.47 (95% CI 2.35-8.59, p < 0.0006) after phototherapy. Heterogeneity in trial design and results precluded meta-analyses for biochemical markers, but a quantitative analysis showed positive results in 13 out of 16 comparisons. The most significant and consistent results were found with red or infrared wavelengths and phototherapy application before exercises, power outputs between 50 and 200 mW and doses of 5 and 6 J per point (spot). We conclude that phototherapy (with lasers and LEDs) improves muscular performance and accelerate recovery mainly when applied before exercise.

Phototherapy is an electrophysical intervention being considered for the retardation of peripheral muscular fatigue usually observed in chronic obstructive pulmonary disease (COPD). The objective of this study was to evaluate the acute effects of combination of super-pulsed laser and light-emitting diodes phototherapy on isokinetic performance in patients with COPD. Thirteen patients performed muscular endurance tests in an isokinetic dynamometer. The maximum voluntary isometric contraction (MVIC), peak torque (PT), and total work (TW) of the non-dominant lower limb were measured in two visits. The application of phototherapy or placebo (PL) was conducted randomly in six locations of femoral quadriceps muscle by using a cluster of 12 diodes (4 of 905 nm super-pulsed lasers, 0.3125 mW each; 4 of 875 nm LEDs, 17.5 mW each; and 4 of 640 nm LEDs, 15 mW each, manufactured by Multi Radiance Medical™). We found statistically significant increases for PT (174.7 ± 35.7 N · m vs. 155.8 ± 23.3 N · m, p = 0.003) and TW after application of phototherapy when compared to placebo (778.0 ± 221.1 J vs. 696.3 ± 146.8 J, p = 0.005). Significant differences were also found for MVIC (104.8 ± 26.0 N · m vs. 87.2 ± 24.0 N · m, p = 0.000), sensation of dyspnea (1 [0-4] vs. 3 [0-6], p = 0.003), and fatigue in the lower limbs (2 [0-5] vs. 5 [0.5-9], p = 0.002) in favor of phototherapy. We conclude that the combination of super-pulsed lasers and LEDs administered to the femoral quadriceps muscle of patients with COPD increased the PT by 20.2% and the TW by 12%. Phototherapy with a combination of super-pulsed lasers and LEDs prior to exercise also led to decreased sensation of dyspnea and fatigue in the lower limbs in patients with COPD.

Modulation of cytochrome c oxidase activity has been pointed as a possible key mechanism for low-level laser therapy (LLLT) in unhealthy biological tissues. But recent studies by our research group with LLLT in healthy muscles before exercise found delayed skeletal muscle fatigue development and improved biochemical status in muscle tissue. Therefore, the aim of this study was to evaluate effects of different LLLT doses and wavelengths in cytochrome c oxidase activity in intact skeletal muscle. In this animal experiment, we irradiated the tibialis anterior muscle of rats with three different LLLT doses (1, 3, and 10 J) and wavelengths (660, 830, and 905 nm) with 50 mW power output. After irradiation, the analyses of cytochrome c oxidase expression by immunohistochemistry were analyzed at 5, 10, 30 min and at 1, 2, 12, and 24 h. Our results show that LLLT increased (p < 0.05) cytochrome c oxidase expression mainly with the following wavelengths and doses: 660 nm with 1 J, 830 nm with 3 J, and 905 nm with 1 J at all time points. We conclude that LLLT can increase cytochrome c oxidase activity in intact skeletal muscle and that it contributes to our understanding of how LLLT can enhance performance and protect skeletal muscles against fatigue development and tissue damage. Our findings also lead us to think that the combined use of different wavelengths at the same time can enhance LLLT effects in skeletal muscle performance and other conditions, and it can represent a therapeutic advantage in clinical settings.

The aim of the present study was to perform a systematic review of the literature on the effects of low-level laser therapy in the treatment of TMD, and to analyze the use of different assessment tools. [Subjects and Methods] Searches were carried out of the BIREME, MEDLINE, PubMed and SciELO electronic databases by two independent researchers for papers published in English and Portuguese using the terms: "temporomandibular joint laser therapy" and "TMJ laser treatment". [Results] Following the application of the eligibility criteria, 11 papers were selected for in-depth analysis. The papers analyzed exhibited considerable methodological differences, especially with regard to the number of sessions, anatomic site and duration of low-level laser therapy irradiation, as well as irradiation parameters, diagnostic criteria and assessment tools. [Conclusion] Further studies are needed, especially randomized clinical trials, to establish the exact dose and ideal parameters for low-level laser therapy and define the best assessment tools in this promising field of research that may benefit individuals with signs and symptoms of TMD.

Background: According to the International Association for the Study of Pain (IASP), the term temporomandibular disorder (TMD) regards a subgroup of orofacial pain, the symptoms of which include pain or discomfort in the temporomandibular joint, ears, masticatory muscles and neck on one or both sides, as well as joint sounds, limited mandibular movements or mandibular deviation and difficulties chewing. Phototherapy, such as low-level laser therapy (LLLT) and light-emitting diode (LED) therapy, is one of the resources used to treatment muscle pain. Thus, there is a need to investigate therapeutic resources that combine different wavelengths as well as different light sources (LLLT and LED) in the same apparatus. The aim of the proposed study is to evaluate the effects of four different doses of phototherapy on pain, activity of the masticatory muscles (masseter and bilateral anterior temporal) and joint mobility in individuals with temporomandibular disorder. A further aim is to determine the cumulative effect 24 and 48 hours after a single session., Methods/design: A placebo-controlled, double-blind, randomized, clinical trial will be carried out involving 72 women between 18 and 40 years of age with a diagnosis of myogenous TMD. The participants will then be randomly allocated to four groups totaling 18 individuals per group. Three groups will be submitted to a single session of phototherapy with different light sources, and one group will receive placebo therapy: Group A (2.62 Joules); Group B (5.24 Joules); Group C (7.86 Joules); and Group D (0 Joules). The following assessment tools will be administered on four separate occasions (baseline and immediately after, 24 h after and 48 h after phototherapy). Pain intensity will be assessed using the visual analog scale for pain, while pain thresholds will be determined using algometer, and electromyographic (EMG) analysis on the masseter and anterior temporal muscles., Discussion: The study will contribute to the practice of the evidence-based use of phototherapy in individuals with a myogenous TMD. Data will be published after the study is completed., Trial Registration: This study is registered with the Brazilian Registry of Clinical Trials, NCT02018770, date of registration: 7 December 2013.

Recent studies with phototherapy have shown positive results in enhancement of performance and improvement of recovery when applied before exercise. However, several factors still remain unknown such as therapeutic windows, optimal treatment parameters, and effects of combination of different light sources (laser and LEDs). The aim of this study was to evaluate the effects of phototherapy with the combination of different light sources on skeletal muscle performance and post-exercise recovery, and to establish the optimal energy dose. A randomized, double-blinded, placebo-controlled trial with participation of 40 male healthy untrained volunteers was performed. A single phototherapy intervention was performed immediately after pre-exercise (baseline) maximum voluntary contraction (MVC) with a cluster of 12 diodes (4 of 905 nm lasers-0.3125 mW each, 4 of 875 nm LEDs-17.5 mW each, and 4 of 670 nm LEDs-15 mW each- manufactured by Multi Radiance Medical™) and dose of 10, 30, and 50 J or placebo in six sites of quadriceps. MVC, delayed onset muscle soreness (DOMS), and creatine kinase (CK) activity were analyzed. Assessments were performed before, 1 min, 1, 24, 48, 72, and 96 h after eccentric exercise protocol employed to induce fatigue. Phototherapy increased (p < 0.05) MVC was compared to placebo from immediately after to 96 h after exercise with 10 or 30 J doses (better results with 30 J dose). DOMS was significantly decreased compared to placebo (p < 0.05) with 30 J dose from 24 to 96 h after exercise, and with 50 J dose from immediately after to 96 h after exercise. CK activity was significantly decreased (p < 0.05) compared to placebo with all phototherapy doses from 1 to 96 h after exercise (except for 50 J dose at 96 h). Pre-exercise phototherapy with combination of low-level laser and LEDs, mainly with 30 J dose, significantly increases performance, decreases DOMS, and improves biochemical marker related to skeletal muscle damage.

Phototherapy with low-level laser therapy (LLLT) and light-emitting diode therapy (LEDT) has arisen as an interesting alternative to drugs in treatments of musculoskeletal disorders. However, there is a lack of studies investigating the effects of combined use of different wavelengths from different light sources like lasers and light-emitting diodes (LEDs) in skeletal muscle disorders. With this perspective in mind, this study aimed to investigate the effects of phototherapy with combination of different light sources on nonspecific knee pain. It was performed a randomized, placebo-controlled, double-blinded clinical trial. Eighty-six patients rated 30 or greater on the pain visual analogue scale (VAS) were recruited and included in study. Patients of LLLT group received 12 treatments with active phototherapy (with 905 nm super-pulsed laser and 875 and 640 nm LEDs, Manufactured by Multi Radiance Medical, Solon, OH, USA) and conventional treatment (physical therapy or chiropractic care), and patients of placebo group were treated at same way but with placebo phototherapy device. Pain assessments (VAS) were performed at baseline, 4th, 7th, and 10th treatments, after the completion of treatments and at 1-month follow-up visit. Quality of life assessments (SF-36®) were performed at baseline, after the completion of treatments and at 1-month follow-up visit. Our results demonstrate that phototherapy significantly decreased pain (p < 0.05) from 10th treatment to follow-up assessments and significantly improved (p < 0.05) SF-36® physical component summary at posttreatments and follow-up assessments compared to placebo. We conclude that combination of super-pulsed laser, red and infrared LEDs is effective to decrease pain and improve quality of life in patients with knee pain.

The wound-healing process plays an essential role in the protective response to epidermal injury by tissue regeneration. In the elderly, skin functions deteriorate as a consequence of morphological and structural changes. This study aimed to evaluate and compare the effect of low-level laser therapy (LLLT) in cutaneous wound healing in young and aged rats. A total of 60 male rats comprising 30 young (± 30 days) and 30 aged (± 500 days) was used. The animals were divided into four experimental groups and underwent skin wound and/or treatment with LLLT (660 nm, 30 mW, 1.07 W/cm(2), 0.028 cm(2), 72 J/cm(2), and 2 J). Analyses were conducted to verify the effects of LLLT in the tissue repair process, in the gene expression, and protein expression of TNF-α, IL-1β, and IL-10, obtained in skin wound model. Results showed that there were significant differences between the young control group and the aged control group and their respective treated groups (LLLT young and LLLT aged). We conclude that LLLT has shown to be effective in the treatment of skin wounds in young and aged animals at different stages of the tissue repair process, which suggests that different LLLT dosimetry should be considered in treatment of subjects of different ages. Further clinical trials are needed to confirm these findings in clinical settings.

This study aimed to evaluate the effects of low-level laser therapy (LLLT) immediately before tetanic contractions in skeletal muscle fatigue development and possible tissue damage. Male Wistar rats were divided into two control groups and nine active LLLT groups receiving one of three different laser doses (1, 3, and 10 J) with three different wavelengths (660, 830, and 905 nm) before six tetanic contractions induced by electrical stimulation. Skeletal muscle fatigue development was defined by the percentage (%) of the initial force of each contraction and time until 50 % decay of initial force, while total work was calculated for all six contractions combined. Blood and muscle samples were taken immediately after the sixth contraction. Several LLLT doses showed some positive effects on peak force and time to decay for one or more contractions, but in terms of total work, only 3 J/660 nm and 1 J/905 nm wavelengths prevented significantly (p < 0.05) the development of skeletal muscle fatigue. All doses with wavelengths of 905 nm but only the dose of 1 J with 660 nm wavelength decreased creatine kinase (CK) activity (p < 0.05). Qualitative assessment of morphology revealed lesser tissue damage in most LLLT-treated groups, with doses of 1-3 J/660 nm and 1, 3, and 10 J/905 nm providing the best results. Optimal doses of LLLT significantly delayed the development skeletal muscle performance and protected skeletal muscle tissue against damage. Our findings also demonstrate that optimal doses are partly wavelength specific and, consequently, must be differentiated to obtain optimal effects on development of skeletal muscle fatigue and tissue preservation. Our findings also lead us to think that the combined use of wavelengths at the same time can represent a therapeutic advantage in clinical settings.

Background: Osteoarthritis is a chronic disease with a multifactor etiology involving changes in bone alignment, cartilage, and other structures necessary to joint stability. There is a need to investigate therapeutic resources that combine different wavelengths as well as different light sources (low-level laser therapy and light-emitting diode therapy) in the same apparatus for the treatment of osteoarthritis. The aim of the proposed study is to analyze the effect of the incorporation of phototherapy into a therapeutic exercise program for individuals with osteoarthritis of the knee., Methods/design: A double-blind, controlled, randomized clinical trial will be conducted involving patients with osteoarthritis of the knee. Evaluations will be performed using functional questionnaires before and after the treatment protocols, in a reserved room with only the evaluator and participant present, and no time constraints placed on the answers or evaluations. The following functional tests will also be performed: stabilometry (balance assessment), dynamometry (muscle strength of gluteus medius and quadriceps), algometry (pain threshold), fleximeter (range of motion), timed up-and-go test (functional mobility), and the functional reach test. The participants will then be allocated to three groups through a randomization process using opaque envelopes: exercise program, exercise program + phototherapy, or exercise program + placebo phototherapy, all of which will last for eight weeks., Discussion: The purpose of this randomized clinical trial is to analyze the effect of the incorporation of phototherapy into a therapeutic exercise program for osteoarthritis of the knee. The study will support the practice based on evidence to the use of phototherapy in individuals with a diagnosis of osteoarthritis of the knee. Data will be published after the study is completed., Trial Registration: The protocol for this study has been submitted to Clinical Trials, registration number NCT02102347, on 29 March 2014.

Osteoarthritis (OA) resulting from injury or disease is associated with increased levels of several matrix metalloproteinases (MMPs), which degrade all components of the complex extracellular matrix in the cartilage. The objective of this study is to investigate the effect of low-level laser therapy (LLLT) on papain-induced joint damage in rats by histopathology and analysis of metalloproteinase 2 and 9 production. Sixty male Wistar rats were randomly distributed into four groups of 15 animals: (1) non-injury negative control, (2) injury positive control, (3) treated with LLLT at 50 mW, and (4) treated with LLLT at 100 mW. OA was induced in animals using papain (4 % solution) followed by treatment with LLLT. After 7, 14, and 21 days, the animals were euthanized. The articular lavage was collected and centrifuged; then, the supernatant was stored prior to protein analysis by western blot. The material was stained with hematoxylin and eosin for histopathological analysis, and Picrosirius Red was used to estimate the percentage of collagen fibers. To determine normal distribution, ANOVA and Tukey's post hoc test were used for comparison between and within each group at each time period. All data are expressed as mean and standard deviation values, with the null hypothesis considered as p < 0.05. Both laser groups (50 and 100 mW) were effective in tissue repair, decreasing collagen type III expression and increasing type I expression in all experimental periods; however, LLLT at 50 mW reduced metalloproteinase 9 more than at 100 mW in 21 days. LLLT at 50 mW was more efficient in the modulation of matrix MMPs and tissue repair.

Synovial membrane inflammation plays an important role in osteoarthritis (OA) pathophysiology. The synovial tissue of patients with initial OA is characterized by mononuclear cell infiltration and the production of pro-inflammatory cytokines and other mediators of joint injury. The study aims to evaluate the effect of low-level laser therapy (LLLT) at doses of 2 and 4 J on joint inflammation in rats induced by papain through histopathological analysis, differential counts of inflammatory cells; gene expression of IL-1β, IL-6, and IL-10; and TNF-α protein expression. Male Wistar rats (20) were randomly divided (5 animals each) into a negative control group, an inflammation injury positive control group, a 2-J LLLT group subjected to injury and treated with 2 J of LLLT, and a 4-J LLLT group subjected to injury and treated with 4 J of LLLT. The animals were subjected to joint inflammation (4 % papain solution) and treated with LLLT. On the day of euthanasia, articular lavage was collected and centrifuged. The supernatant was analyzed for TNF-α protein expression by ELISA and IL-1β, IL-6, and IL-10 mRNA by RT-PCR. The joint tissue was also examined histologically. ANOVA with Tukey's post hoc test was used for comparisons. All data were expressed as means ± S.D. (p < 0.05). Both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1β and IL-6. However, the 2-J treatment led to more reduction in TNF-α than the 4-J treatment. A single application of LLLT with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells.

Background: Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes., Methods/design: A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109., Discussion: The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index - normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed.