Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD.

Introduction: Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model. Methods: We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p < 0.05). Results: This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells. Conclusion: This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD.

Photobiomodulation mitigates Bothrops jararacussu venom-induced damage in myoblast cells by enhancing myogenic factors and reducing cytokine production.

BACKGROUND: Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: C2C12 myoblast cells were exposed to BjsuV (12.5 µg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кß, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-ß, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-ß, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP. CONCLUSION/SIGNIFICANCE: These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process.

Photobiomodulation in promoting increased Skin Flap Viability: a systematic review of animal studies.

Necrosis is common in skin flap surgeries. Photobiomodulation, a noninvasive and effective technique, holds the potential to enhance microcirculation and neovascularization. As such, it has emerged as a viable approach for mitigating the occurrence of skin flap necrosis. The aim of this systematic review was to examine the scientific literature considering the use of photobiomodulation to increase skin-flap viability. The preferred reporting items for systematic reviews and meta-analyses (PRISMA), was used to conducted systematic literature search in the databases PubMed, SCOPUS, Elsevier and, Scielo on June 2023. Included studies investigated skin-flap necrosis employing PBMT irradiation as a treatment and, at least one quantitative measure of skin-flap necrosis in any animal model. Twenty-five studies were selected from 54 original articles that addressed PBMT with low-level laser (LLL) or light-emitting diode (LED) in agreement with the qualifying requirements. Laser parameters varied markedly across studies. In the selected studies, the low-level laser in the visible red spectrum was the most frequently utilized PBMT, although the LED PBMT showed a similar improvement in skin-flap necrosis. Ninety percent of the studies assessing the outcomes of the effects of PBMT reported smaller areas of necrosis in skin flap. Studies have consistently demonstrated the ability of PBMT to improve skin flap viability in animal models. Evidence suggests that PBMT, through enhancing angiogenesis, vascular density, mast cells, and VEGF, is an effective therapy for decrease necrotic tissue in skin flap surgery.

Effect of systemic photobiomodulation in the course of acute lung injury in rats.

Acute lung injury (ALI) is a severe, multifactorial lung pathology characterized by diffuse alveolar injury, inflammatory cell infiltration, alveolar epithelial barrier rupture, alveolar edema, and impaired pulmonary gas exchange, with a high rate of mortality; and sepsis is its most common cause. The mechanisms underlying ALI due to systemic inflammation were investigated experimentally by systemic lipopolysaccharide (LPS) administration. Photobiomodulation (PBM) has been showing good results for several inflammatory diseases, but there are not enough studies to support the real benefits of its use, especially systemically. Considering that ALI is a pathology with high morbidity and mortality, we studied the effect of systemic PBM with red light-emitting diode (LED) (wavelength 660 nm; potency 100 mW; energy density 5 J/cm; total energy 15 J; time 150 s) in the management of inflammatory parameters of this disease. For this, 54 male Wistar rats were submitted to ALI by LPS injection (IP) and treated or not with PBM systemically in the tail 2 and 6 h after LPS injection. Data were analyzed by one-way ANOVA followed by Student's Newman-Keuls. Our results point to the beneficial effects of systemic PBM on the LPS-induced ALI, as it reduced the number of neutrophils recruited into the bronchoalveolar lavage, myeloperoxidase activity, and also reduced interleukins (IL) 1ß, IL-6, and IL-17 in the lung. Even considering the promising results, we highlight the importance of further studies to understand the mechanisms involved, and especially the dosimetry, so that in near future, we can apply this knowledge in clinical practice.

Prenatal programming of the immune response induced by maternal periodontitis: Effects on the development of acute lung injury in rat pups.

AIMS: Oral cavity pathogens play an important systemic role, modulating the development of several diseases. Periodontitis is a very common oral disease associated with dental biofilm. It is characterized by gum inflammation, periodontal ligament degeneration, dental cementum and alveolar bone loss. Studies point to the association between maternal periodontitis and adverse outcomes during pregnancy. However, they did not evaluate the impact of maternal periodontitis in the offspring. Thus, our objective was to investigate the effects of maternal periodontitis in the immune system of offspring. MATERIAL AND METHODS: For this evaluation we induced acute lung injury in rat pups. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after the birth, offspring was submitted to acute lung inflammation by administration of lipopolysaccharide (LPS, Salmonella abortus equi, 5 mg/kg, ip). KEY FINDINGS: Our results showed that maternal periodontitis increased myeloperoxidase activity, the levels of TNF-alpha and IL-17A in the bronchoalveolar fluid, the gene expression of TNF-alpha, IL-17A, and cyclooxygenases 1 and 2. In addition, maternal periodontitis did not alter the number of leukocytes migrated into the lung, tracheal responsiveness, expression of TLR4 and NF-KB translocation. SIGNIFICANCE: This study showed prenatal programming of the immune response induced by maternal periodontitis, and reinforces the importance of oral health care during pregnancy.

Effect of 12 Weeks of Endurance Training Combined with Creatine Supplement, Photobiomodulation Therapy, or Both on Performance and Muscle Damage in Rats.

Background: Photobiomodulation therapy (PBMT) and creatine (Cr) intake have been used in conjunction with heavy training, but little is known about their possible effects during a long-term training program. Objective: We assessed long-term use of PBMT and Cr in an exercise training program. Methods: Twenty-five male Wistar rats weighing ∼300 g were randomly allocated to one of five groups: a nontraining control group, a training group, a training group receiving Cr, a training group receiving PBMT, and a training group receiving both PBMT and Cr. The training program consisted of 12 weeks of daily swimming training. PBMT was delivered in six points with a laser device (808 nm, 100 mW, 30 sec per point of irradiation, 3 J, 75 J/cm2). Results: All training groups showed significantly higher peak force and longer time to 50% decay of force, and lower creatine kinase (CK) levels than the nontraining control group, thus confirming the benefit of the training program. In all outcomes related to muscle performance, the groups receiving PBMT with or without Cr supplement performed significantly better (p < 0.05) peak force and time of force decay during an electrical stimulation protocol than all the other groups. In addition, CK levels were also significantly lower for the PBMT groups than for the other groups. Conclusions: We conclude that PBMT alone or in conjunction with Cr supplement during a 12-week training program resulted in significantly better muscle performance and lower levels of CK, a biochemical marker of muscle damage.

PBMT and topical diclofenac as single and combined treatment on skeletal muscle injury in diabetic rats: effects on biochemical and functional aspects.

Physical exercise generates several benefits in a short time in patients with diabetes mellitus. However, it can increase the chances of muscle damage, a serious problem for diabetic patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat these injuries, despite the serious adverse effects. In this way, photobiomodulation therapy (PBMT) with low-level laser therapy (LLLT) and/or light emitting diode therapy (LEDT) can be used as an alternative in this case. However, its efficacy in tissue repair of trauma injuries in diabetes mellitus until now is unknown, as well as the combination between PBMT and NSAIDs. The objective of the present study was to evaluate the effects of NSAIDs and PBMT applied alone or combined on functional and biochemical aspects, in an experimental model of muscle injury through controlled trauma in diabetic rats. Muscle injury was induced by means of a single trauma to the animals' anterior tibialis muscle. After 1 h, the rats were treated with PBMT (830 nm; continuous mode, with a power output of 100 mW; 3.57 W/cm2; 3 J; 107.1 J/cm2, 30 s), diclofenac sodium for topical use (1 g), or combination of them. Our results demonstrated that PBMT + diclofenac, and PBMT alone reduced the gene expression of cyclooxygenase-2 (COX-2) at all assessed times as compared to the injury and diclofenac groups (p < 0.05 and p < 0.01 respectively). The diclofenac alone showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). Prostaglandin E2 levels in blood plasma demonstrated similar results to COX2. In addition, we observed that PBMT + diclofenac and PBMT alone showed significant improvement compared with injury and diclofenac groups in functional analysis at all time points. The results indicate that PBMT alone or in combination with diclofenac reduces levels of inflammatory markers and improves gait of diabetic rats in the acute phase of muscle injury.

Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats: Effects of Laser Photobiomodulation.

BACKGROUND: Unusual and exhaustive physical exercise can lead to muscle lesions depending on the type of contraction, intensity, duration, age, and level of conditioning. Different therapies have been proposed to prevent or reduce exercise-induced muscle damage. OBJECTIVE: In this study, we investigate the effects of low-level laser therapy on skeletal muscle strain in an experimental model in rats. MATERIALS AND METHODS: Male Wistar rats (200 g) were used. The animals were randomized into groups of six animals. We performed tibialis muscle elongation using a previously described protocol. The animals were anesthetized and submitted to passive stretching of the anterior tibial muscle attached to a weight corresponding to 150% of the body mass of the animal for 20 min, rested for 3 min, and received a second traction for 20 min. The cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and IL-10, edema, and C-reactive protein (CRP) levels were determined in the tibialis anterior muscle. RESULTS: Plasma extravasation of groups treated with different doses of laser energy, lesion +1 J (2.61 ± 0.46), lesion +3 J (2.33 ± 0.13), lesion +6 J (2.92 ± 0.91), and lesion +9 J (2.80 ± 0.55), shows a significant reduction of extravasation when compared with the injury group (5.46 ± 1.09). Laser therapy was able to significantly reduce CRP and cytokine levels (TNF-α, IL-1ß, IL-6, and IL-10). CONCLUSIONS: Laser photobiomodulation reduced skeletal muscle edema as well as cytokines and CRP, leading to a significant reduction in inflammatory markers.

Photobiomodulation therapy (PBMT) on acute pain and inflammation in patients who underwent total hip arthroplasty-a randomized, triple-blind, placebo-controlled clinical trial.

When conservative treatments fail, hip osteoarthritis (OA), a chronic degenerative disease characterized by cartilage wear, progressive joint deformity, and loss of function, can result in the need for a total hip arthroplasty (THA). Surgical procedures induced tissue trauma and incite an immune response. Photobiomodulation therapy (PBMt) using low-level laser therapy (LLLT) and/or light-emitting diode therapy (LEDT) has proven effective in tissue repair by modulating the inflammatory process and promoting pain relief. Therefore, the aim of this study was to analyze the immediate effect of PBMt on inflammation and pain of patients undergoing total hip arthroplasty. The study consisted of 18 post-surgical hip arthroplasty patients divided into two groups (n = 9 each) placebo and active PBMt who received one of the treatments in a period from 8 to 12 h following THA surgery. PBMt (active or placebo) was applied using a device consisting of nine diodes (one super-pulsed laser of 905 nm, four infrared LEDs of 875 nm, and four red LEDs 640 nm, 40.3 J per point) applied to 5 points along the incision. Visual analog scale (VAS) and blood samples for analysis of the levels of the cytokines TNF-α, IL-6, and IL-8 were recorded before and after PBMt application. The values for the visual analog scale as well as those in the analysis of TNF-α and IL-8 serum levels decreased in the active PBMt group compared to placebo-control group (p < 0.05). No decrease was observed for IL-6 levels. We conclude that PBMt is effective in decreasing pain intensity and post-surgery inflammation in patients receiving total hip arthroplasty.

High doses of laser phototherapy can increase proliferation in melanoma stromal connective tissue.

It is well established that laser phototherapy (LP) is contraindicated directly over cancer cells, due to its bio modulatory effects in cell and blood vessel proliferation. The aim of the present study was to analyze the influence of typical low-level laser therapy (LLLT) and high intensity laser therapy (HILT) and an in-between dose of 9 J on collagen fibers and blood vessels content in melanoma tumors (B16F10) implanted in mice. Melanoma tumor cells were injected in male Balb C mice which were distributed in four groups: control (no irradiated) or irradiated by 3, 9, or 21 J (150; 450, or 1050 J/cm2). LP was performed in daily sessions for 3 days with a InGaAlP-660 nm (mean output: 50 mW, spot size: 2 mm2). Tumor volume was analyzed using (1) picrosirius staining to quantify collagen fibers content and (2) Verhoeff's method to quantify blood vessels content. Tumor growth outcome measured in the 3-J group was not significantly different from controls. Nine and 21-J groups, presented significant and dose-dependent increases in tumor volume. Quantitative analysis of the intensity of collagen fibers and their organization in stroma and peri-tumoral microenvironment showed significant differences between irradiated and control group. Blood vessels count of 21-J group outnumbered the other groups. High doses (≥ 9 J) of LP showed a dose-dependent tumor growth, different collagen fibers characteristics, and eventually blood vessel growth, while a typical LLLT dose (3 J) appeared harmless on melanoma cell activity.

Comparison of Photobiomodulation and Anti-Inflammatory Drugs on Tissue Repair on Collagenase-Induced Achilles Tendon Inflammation in Rats.

BACKGROUND: Tendinopathy is characterized by pain, edema, and structural changes in tendon tissue. OBJECTIVE: In this animal study we decided to compare the short- and medium-term effects of low-level laser therapy (LLLT), dexamethasone, and diclofenac on inflammation and tendon tissue repair in collagenase-induced tendinitis. MATERIALS AND METHODS: Two hundred five female Wistar rats were randomly divided into five groups. Animals in the control group were given a saline injection and the experimental groups received a collagenase injection (100 µg/tendon) in the peritendinous Achilles and received no treatment, LLLT (3 J, 810 nm, 100 mW), diclofenac (1.1 mg/kg), or dexamethasone (0.02 mg/kg). Histological analyses were performed at 10 time points up to 60 days (n = 5/group each time point), and included an assessment of the severity of inflammation, collagen fiber content, and organization. RESULTS: Collagenase injection induced a severe inflammatory reaction with significant reduction in collagen content for 48 h, and disorientation of collagen fibers lasting between 14 and 21 days. Diclofenac and dexamethasone reduced inflammatory signs during the first 2 days, although there was prolongation of the inflammatory phase and slower normalization of tendon quality, particularly in the dexamethasone group. LLLT prevented hemorrhage, reduced inflammation severity, and preserved tendon morphology compared with the other groups. CONCLUSIONS: LLLT showed a significant superiority over commonly used anti-inflammatory pharmaceutical agents in acute collagenase-induced tendinitis.

Photobiomodulation therapy protects skeletal muscle and improves muscular function of mdx mice in a dose-dependent manner through modulation of dystrophin.

This study aimed to analyze the protective effects of photobiomodulation therapy (PBMT) with combination of low-level laser therapy (LLLT) and light emitting diode therapy (LEDT) on skeletal muscle tissue to delay dystrophy progression in mdx mice (DMD mdx ). To this aim, mice were randomly divided into five different experimental groups: wild type (WT), placebo-control (DMD mdx ), PBMT with doses of 1 J (DMD mdx ), 3 J (DMD mdx ), and 10 J (DMD mdx ). PBMT was performed employing a cluster probe with 9 diodes (1 x 905nm super-pulsed laser diode; 4 x 875nm infrared LEDs; and 4 x 640nm red LEDs, manufactured by Multi Radiance Medical®, Solon - OH, USA), 3 times a week for 14 weeks. PBMT was applied on a single point (tibialis anterior muscle-bilaterally). We analyzed functional performance, muscle morphology, and gene and protein expression of dystrophin. PBMT with a 10 J dose significantly improved (p < 0.001) functional performance compared to all other experimental groups. Muscle morphology was improved by all PBMT doses, with better outcomes with the 3 and 10 J doses. Gene expression of dystrophin was significantly increased with 3 J (p < 0.01) and 10 J (p < 0.01) doses when compared to placebo-control group. Regarding protein expression of dystrophin, 3 J (p < 0.001) and 10 J (p < 0.05) doses also significantly showed increase compared to placebo-control group. We conclude that PBMT can mainly preserve muscle morphology and improve muscular function of mdx mice through modulation of gene and protein expression of dystrophin. Furthermore, since PBMT is a non-pharmacological treatment which does not present side effects and is easy to handle, it can be seen as a promising tool for treating Duchenne's muscular dystrophy.

Laser photobiomodulation of pro-inflammatory mediators on Walker Tumor 256 induced rats.

Laser photobiomodulation or low-level laser therapy (LLLT) is recognized worldwide for its expansive use in medicine. LLLT has been reported to increase enzymatic activity, increasing the mitochondrial transmembrane potential, leading to an increased energy availability and signal transduction. Nevertheless, an inhibitory effect is also observed by the production of excessive ROS which can result the shutdown of mitochondrial energy production, and finally to apoptosis. However, the mechanism of apoptosis induced by LLLT is still not well understood. The main objective of the present study was to investigate the hypothesis that LLLT induces oxidative stress and stimulates the generation of pro-inflammatory markers interfering in tumor progression. METHODS: Seventy-two female Walker Tumor induced Wistar rats (eight weeks of age, 200g body weight) were used for this study. TW-256 cells were suspended in phosphate buffered saline and then subcutaneously inoculated at 1×107viabletumorcells/ml per rat into the right flank (tumor-bearing rats). After a period of 14days in order to assess the development of the solid tumor mass, the animals were randomized and distributed in four groups (n=8 animals/group): (1) Control or irradiated by LLLT (2) Laser 1J - 35,7J/cm2, (3) Laser 3J - 107,14J/cm2 and (4) Laser 6J - 214,28J/cm2; (Thera Laser - 660nm, 100mW DMC®, São Carlos, Brazil) at four equidistant points according to their respective treatment groups, conducted three times on alternate days. The regulation and expression of inflammatory mediators IL-1ß, IL-6, IL-10, TNF-α was assessed by ELISA and gene expression of COX-1, COX-2, iNOS, eNOS was analyzed by RT-PCR. RESULTS: We found that the 1Joule (J) treated group promoted a significant increase in the levels of different inflammatory markers IL-1ß, the gene expression of COX-2, iNOS, which was statistically different (p<0.05) when compared among different treatment and control groups. With Respect IL-6, IL-10, TNF-α levels statistically significant reduce was observed in 1Joule treated group when comparing to different energies groups and control group. CONCLUSION: Our results suggest the evidence 1J-35,7J/cm2 treatment was able to produce cytotoxic effects by generation of ROS causing acute inflammation and thus may be employed as the best energy dose associated with Photodynamic Therapy.

Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 2: biochemical aspects.

Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm2; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm2), 3 J (107.1 J/cm2), and 9 J (321.4 J/cm2) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p < 0.05). The diclofenac group showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). COX-2 protein expression remained unchanged with all therapies except with PBMT at a 3-J dose at 12 h (p < 0.05 compared to the injury group). In addition, PBMT (1, 3, and 9 J) effectively reduced levels of cytokines TNF-α, interleukin (IL)-1ß, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p < 0.05). Thus, PBMT at a 3-J dose was more effective than other doses of PBMT and topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.

Effects of low-level laser therapy on the modulation of tissue temperature and hyperalgesia following a partial Achilles tendon injury in rats.

The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) on the modulation of tissue temperature and hyperalgesia following a partial injury to the Achilles tendon in rats. Forty-five rats were randomly divided into three groups: a control group, a group treated with LLLT at a dose of 1.4 J (808 nm, 50 mW, 1.4 J), and a group treated with LLLT at a dose of 2.1 J (808 nm, 50 mW, 2.1 J). LLLT was administered to a single point immediately following the partial injury of the Achilles tendon. Tissue temperature and hyperalgesia were evaluated 6, 24, and 48 hours following the injury. Thus, a significant group-versus-time interaction was found for tissue temperature (F = 4.097, p = 0.001) and hyperalgesia (F = 106.605, p < 0.001), with a greater reduction in theses outcomes in the group that received LLLT at a dose of 2.1 J evaluated 48 hours after the injury. Therefore, LLLT at a wavelength of 808 nm and dose of 2.1 J administered immediately following a partial injury to the Achilles tendon led to a reduction in tissue temperature and hyperalgesia at the injury site in rats, especially 48 hours after injury.

Light-Emitting Diode treatment ameliorates allergic lung inflammation in experimental model of asthma induced by ovalbumin.

Since asthma is a multifactorial disease where treatment sometimes is not effective, new therapies that improve the respiratory discomfort of patients are of great importance. Phototherapy as Light-emitting diode (LED) has emerged as a treatment that presents good results for diseases that are characterized by inflammation. Thus, our objective was to investigate the effects of LED on lung inflammation, by an evaluation of lung cell infiltration, mucus secretion, oedema, and the production of cytokines. Male Balb/c mice were or not sensitized and challenged with ovalbumin (OVA) and treated or not with LED therapy (1 h and 4 h after each OVA challenge). Twenty-four hours after the last OVA challenge, analyzes were performed. Our results showed that LED treatment in asthmatic mice reduced the lung cell infiltration, the mucus production, the oedema, and the tracheal's contractile response. It also increased the IL-10 and the IFN-gamma levels. The effects of LED treatment on lung inflammation may be modulated by IL-10, IFN-gamma, and by mast cells. This study may provide important information about the effects of LED, and in addition, it may open the possibility of a new approach for the treatment of asthma.

Photobiomodulation therapy in the modulation of inflammatory mediators and bradykinin receptors in an experimental model of acute osteoarthritis.

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/cm2), laser beam (0.028 cm2), and energy density (144 J/cm2)-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.

Low-Level Laser Therapy and Cryotherapy as Mono- and Adjunctive Therapies for Achilles Tendinopathy in Rats.

BACKGROUND AND OBJECTIVE: Low-level laser therapy (LLLT) and cryotherapy are widely used treatments in the acute phase of tendon injury. The aim of this study was to investigate the interaction of these two treatments on tendon inflammation and mechanical properties. MATERIALS AND METHODS: Six groups of six Wistar rats were used in this study. The Achilles tendons of the healthy control group were not subjected to injury or treatment. The tendons of the injured nontreated group (ING) were injured, but not treated. The remaining four groups were injured and subjected to LLLT, cryotherapy, LLLT first/cryotherapy, or cryotherapy first/LLLT. All treatments were performed at 1 h post-trauma. Inflammatory mediators, tendon histology, and biomechanical properties were assessed at 24 h post-trauma by comparing the treatment groups with the ING. RESULTS: In all treatment groups, the inflammatory process shifted in an anti-inflammatory direction compared with the ING. Significant alterations in cytokine expression were found in only the LLLT group (↓IL-1ß) and the combined intervention groups (↓IL-1ß, ↓TNF-α, ↑IL-6). It was also found that cryotherapy followed by LLLT was the only treatment that significantly (p < 0.05) improved the biomechanical parameters of force (N) and displacement (mm) at the tendon rupture and corresponded with the best histological scores of all of the treatment groups. CONCLUSIONS: Our results demonstrate that cryotherapy in combination with LLLT can produce an anti-inflammatory "add-on" effect. The order of therapy administration seems essential, as superior histology and biomechanical results were found in the cryotherapy first/LLLT group.