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.

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.

Effects of photobiomodulation therapy, pharmacological therapy, and physical exercise as single and/or combined treatment on the inflammatory response induced by experimental osteoarthritis.

Osteoarthritis (OA) triggers increased levels of inflammatory markers, including prostaglandin (PG) E2 and proinflammatory cytokines. The elevation of cytokine levels is closely associated with increased articular tissue degeneration. Thus, the use of combination therapies may presumably be able to enhance the effects on the modulation of inflammatory markers. The present study aimed to evaluate and compare the effects of photobiomodulation therapy (PBMT), physical exercise, and topical nonsteroidal anti-inflammatory drug (NSAID) use on the inflammatory process after they were applied either alone or in different combinations. OA was induced by intra-articular papain injection in the knee of rats. After 21 days, the animals began treatment with a topical NSAID and/or with physical exercise and/or PBMT. Treatments were performed three times a week for eight consecutive weeks, totaling 24 therapy sessions. Analysis of real-time polymerase chain reaction (RT-PCR) gene expression; interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) protein expression; and PGE2 levels by enzyme-linked immunosorbent assay (ELISA) was conducted. Our results showed that PBMT alone and Exerc + PBMT significantly reduced IL-1ß 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-1ß protein expression (p < 0.05). All therapies significantly reduced IL-6 and TNF-α protein expression (p < 0.05) compared with the OA group. Similarly, all therapies, except Exerc, reduced the levels of PGE2 (p < 0.05) compared with the OA group. The results from the present study indicate that treatment with PBMT is more effective in modulating the inflammatory process underlying OA when compared with the other therapies tested.

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.

The low level laser therapy (LLLT) operating in 660 nm reduce gene expression of inflammatory mediators in the experimental model of collagenase-induced rat tendinitis.

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.

Effect of simvastatin on passive strain-induced skeletal muscle injury in rats.

INTRODUCTION: HMG-CoA reductase inhibitors are the most frequently prescribed drugs for treatment of lipid imbalance, but they have side effects, such as myopathy. Our aim was to assess the effect of simvastatin on the inflammatory process induced by skeletal muscle injury. METHODS: Rats were divided into experimental groups [control group, simvastatin (20 mg/kg) group, group treated with simvastatin (20 mg/kg) and subjected to injury, and group subjected to injury only]. Histological analysis and analyses of creatine kinase activity and C-reactive protein were performed. RESULTS: Animals treated with simvastatin exhibited significantly greater morphological and structural skeletal muscle damage in comparison to the control group and injured animals without treatment. CONCLUSIONS: Although simvastatin has a small anti-inflammatory effect in the early stage after a muscle strain injury, the overall picture is negative, as simvastatin increases the extent of damage to muscle morphology. Further studies are needed.

Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation.

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.

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.

Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain.

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.

Comparative Study of the Physiotherapeutic and Drug Protocol and Low-Level Laser Irradiation in the Treatment of Pain Associated with Temporomandibular Dysfunction.

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/cm2, 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.

Infrared (810 nm) low-level laser therapy in experimental model of strain-induced skeletal muscle injury in rats: effects on functional outcomes.

Muscle strains are among the most prevalent causes for athletes' absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats.

Infrared (810 nm) low-level laser therapy in rat achilles tendinitis: a consistent alternative to drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used and can reduce musculoskeletal pain in spite of the cost of adverse reactions like gastrointestinal ulcers or cardiovascular events. The current study investigates if a safer treatment such as low-level laser therapy (LLLT) could reduce tendinitis inflammation, and whether a possible pathway could be through inhibition of either of the two-cyclooxygenase (COX) isoforms in inflammation. Wistar rats (six animals per group) were injected with saline (control) or collagenase in their Achilles tendons. Then, we treated them with three different doses of IR LLLT (810 nm; 100 mW; 10 s, 30 s and 60 s; 3.57 W cm(-2); 1 J, 3 J, 6 J) at the sites of the injections, or intramuscular diclofenac, a nonselective COX inhibitor/NSAID. We found that LLLT dose of 3 J significantly reduced inflammation through less COX-2-derived gene expression and PGE(2) production, and less edema formation compared to nonirradiated controls. Diclofenac controls exhibited significantly lower PGE(2) cytokine levels at 6 h than collagenase control, but COX isoform 1-derived gene expression and cytokine PGE(2) levels were not affected by treatments. As LLLT seems to act on inflammation through a selective inhibition of the COX-2 isoform in collagenase-induced tendinitis, LLLT may have potential to become a new and safer nondrug alternative to coxibs.