Customized Photobiomodulation Modulates Pain and Alters Thermography Pattern in Patients with Knee Osteoarthritis: A Randomized Double-Blind Pilot Study.

Background: Photobiomodulation therapy (PBMT) modulates a wide variety of biological processes, leading to anti-inflammatory and analgesic effects. Understanding the mechanisms underlying therapeutic effects of PBMT remains challenging due to varying outcomes observed between wavelengths, dosage, and site of application. Our research group has dedicated close attention to customization and individualization of dosimetry for PBMT protocols. Preliminary data showed that using an individualized treatment could solve contradictory results reported by previous studies. Based on literature and our preliminary data on light absorption, the goal of the present pilot is to determine whether our individualized dosimetry is a feasible method to assist osteoarthritis (OA) pain control. Methods: This parallel two-arm controlled-pilot study aimed to assess whether personalized PBMT can be effective in the treatment of painful chronic knee OA. Thirty-one patients were randomly allocated into treatment and placebo group (sham irradiation), and the treatment procedure was performed twice a week, for 5 weeks. The PBMT was applied using 850 nm with continuous wave and a total of 526-1402 J each session. Individualized dosimetry was chosen based on each patient's body mass index and skin color. Quality-of-life (QOL) questionnaires and serum/urine analyses were performed before and after treatment was over. Both examiners and participants were blinded to group allocation. Results: Pain scores were reduced significantly in the 4th, 5th, and 10th sessions and remained lower 6 weeks posttherapy in the treatment group when compared to the placebo group. Moreover, the treatment group's results were improved in QOL questionnaires score, dopamine level, and in microcirculation. Conclusions: The present results provide initial evidence that customized photobiomodulation (PBM) reduce pain levels in short- and medium-term in patients with symptomatic knee OA when compared to placebo group. Furthermore, we have provided evidence that customized PBM is able to improve the QOL of those patients.

Effects of photobiomodulation therapy in chondrocyte response by in vitro experiments and experimental model of osteoarthritis in the knee of rats.

The purpose of this study is to evaluate the effects of photobiomodulation (PBM) therapy in chondrocyte response by in vitro experiments and cartilage repair using an experimental model of osteoarthritis (OA) in the knee of rats. The in vitro experiment was performed with chondrocyte cells, and they were divided into two groups: non-irradiated and irradiated with PBM (808 nm; 0.8 J or 1.4 J). Then, cell proliferation was evaluated after 1, 3, and 5 days. The experimental model of osteoarthritis (OA) was performed in the knee of 64 Wistar rats, and they were assorted into control group (CG), PBM (808 nm; 1.4 J). The results of in vitro showed that PBM 1.4 J increased cell proliferation, on days 1 and 5. However, after 3 days was demonstrated a significant increase in cell proliferation in PBM 0.8 J. The in vivo experiment results demonstrated, on histological analysis, that PBM presented less intense signs of tissue degradation with an initial surface discontinuity at the superficial zone and disorganization of the chondrocytes in the cartilage region when compared to CG, after 4 and 8 weeks. These findings were confirmed by immunohistochemistry and qRT-PCR analysis which showed that PBM increased IL-4, IL-10, COL-2, Aggrecan, and TGF-ß which are anabolic factors and acts on extracellular matrix. Also, PBM reduces the IL1-ß, an inflammatory marker that operates as a catabolic factor on articular cartilage. In conclusion, these results suggest that PBM may have led to a return to tissue homeostasis, promoting chondroprotective effects and stimulating the components of the articular tissue.

Photobiomodulation and Sida tuberculata combination declines the inflammation's markers in knee-induced osteoarthritis.

The aim of this study was to assess potential combination effects of photobiomodulation therapy (PBMT) with Sida tuberculata extracts on the oxidative stress and antioxidant activity, as well as on the inflammatory process. Rats with knee osteoarthritis (OA) were treated with S. tuberculata extracts and PBMT (904 nm, 18 J/cm2). The animals were evaluated for nociception and edema. The blood, knee lavage and structures, spinal cord, and brainstem were collected for biochemical analyses (lipid peroxidation, protein carbonyl content, superoxide dismutase activity, non-protein thiol levels, and measurement of nitrite/nitrate). The knee structures were also used to measure cytokine levels. PBMT lowered the damage due to oxidative stress in the knee and at distant sites from the lesion. PBMT also reduced the levels of nitric oxide and cytokines, which could explain the nociception reduction mechanism. Similarly, S. tuberculata decreased the damage by oxidative stress, levels of nitrite/nitrate, and cytokines. The therapy combination reduced levels of cytokines and nitrite/nitrate. PBMT and S. tuberculata extracts reduced the oxidative stress and inflammation. It is noteworthy that PBMT increased the antioxidant activity in the knee and at sites distant from the lesion, contributing to a more significant decrease in nociception. The combination of therapies did not present significant effects on the analyzed parameters. Therefore, it is suggested that PBM is sufficient to minimize the signs and symptoms of the knee OA in our rat model.

Photobiomodulation Therapy (Light-Emitting Diode 630 nm) Favored the Oxidative Stress and the Preservation of Articular Cartilage in an Induced Knee Osteoarthritis Model.

Objective: To evaluate the effects of photobiomodulation (PBM) therapy on oxidative stress and histological aspects of knee osteoarthritis (OA) induced by sodium monoiodoacetate in Wistar rats. Background: OA is a chronic degenerative disease. In addition to the inflammatory role, other factors, such as redox balance, appear to contribute to changes in the articular cartilage, the main articular structure affected. PBM therapy using light-emitting diode (LED) has been proposed to treat the disease by favoring anti-inflammatory effects and modulating markers of oxidative stress, acting on the degenerative process of cartilage. Methods: Twenty-seven male rats were separated into three groups: control (CG), OA (OAG), and LED treatment (LEDG). In the LED group, PBM (LED 630 nm, 300 mW, 9 J/cm2, 0.3 W/cm2, 30 sec) was applied, starting 24 h after induction, three times per week, for 8 weeks. Cartilage thickness, number of chondrocytes, enzymatic antioxidant defenses [superoxide dismutase (SOD) and catalase (CAT)], oxidative damage [thiobarbituric acid reactive substances (TBARS)], and nonenzymatic defense (ferric reducing antioxidant power) were analyzed. Results: The LEDG had higher average cartilage thickness compared with the OAG and had similar thickness to the CG. Also, the number of chondrocytes was similar to the CG. In the oxidative stress analysis, the LEDG presented antioxidant enzymatic activity (SOD and CAT) higher than the CG, and presented concentration of TBARS lower than the CG and OAG groups. Conclusions: PBM therapy was effective in recovering oxidative stress and preserving the articular cartilage aspects in a knee OA animal model.

Association of photobiomodulation therapy (PBMT) and exercises programs in pain and functional capacity of patients with knee osteoarthritis (KOA): a systematic review of randomized trials.

Knee osteoarthritis (KOA) is a common degenerative disease in which several treatments and treatment associations have been investigated. This review analyzed the efficacy of the association of photobiomodulation therapy (PBMT) and exercises for people with KOA in randomized controlled clinical trials. PubMed, Scopus, and EMBASE databases were searched using the following terms: "knee osteoarthritis," "laser," "low-level laser," "photobiomodulation," "phototherapy," and "exercise." Seven RCT studies involving humans that examined PBMT treatment in association with were found. Most studies used mainly near-infrared PBMT irradiation, with a fluence ranging from 610 mJ/cm2 to 200 J/cm2, 23.55 J to 2400 J total energy per knee, and number of treatment sessions from 10 to 24. In addition, all the protocols included exercises to increase lower limb muscle strength that were performed alone or in association with other types of exercises. However, only 2 studies, considered as a high quality, showed the additional effect of PBMT (lower doses) on an exercise program (involving warming-up, motor learning, balance coordination and strengthening exercises, and stretching) for improvement of pain and functional capacity in people with KOA. This review demonstrates that there is a controversy on the effects PBMT associated with exercises for pain and functional capacity improvement for people with KOA, because there is a heterogeneity between studies in related to PBMT parameters, as dose, number of therapy sessions and the type of PBMT (either LLLT and HILT), and the exercise protocols proposed.

Level of pain, muscle strength and posture: effects of PBM on an exercise program in women with knee osteoarthritis - a randomized controlled trial.

To evaluate the effectiveness of an exercise program associated to photobiomodulation (PBM) on pain, postural changes, functionally, and muscular strength in women, one of the risk factors, with knee osteoarthritis (OA). A randomized controlled trial, with a blinded assessor and intention-to-treat analysis and placebo control. Sixty-two participants with knee OA (with confirmed radiological diagnosis) were evaluated for this study. However, 34 were considered eligible and were randomized into two groups: EPPG - exercise and PBM placebo group (n = 17) and EPAG - exercise and PBM active group (n = 16), but one participant was excluded of EPAG. The exercise program and PBM (808 nm, 100 mW/point, 4 J/point, 56 J total, 91 J/cm2) were realized twice a week, during 8 weeks. West Ontario and the McMaster University Osteoarthritis Index (WOMAC) and Lequesne questionnaires, 1-repetition maximum test (1-RM) and posture evaluation software (SAPO) were used to analyze the effects of the therapies. In intragroup analysis, a significant improvement in pain WOMAC (p < 0.001), stiffness (p < 0.001), function (p < 0.001), Lequesne (p < 0.001), and 1-RM (all muscle groups) (p < 0.001) were observed. In this study, the exercise program improved pain, function, and muscle strength of all the participants. However, PBM, in the parameters used, did not optimize the effects of the exercise program in women with knee OA.

Photobiomodulation via a cluster device associated with a physical exercise program in the level of pain and muscle strength in middle-aged and older women with knee osteoarthritis: a randomized placebo-controlled trial.

Osteoarthritis (OA) is a chronic joint disease that leads to pain and functional incapacity. The aim of the study is to investigate the effects of the incorporation of photobiomodulation (PBM) (via cluster) into a physical exercise program on the level of pain, lower limb muscle strength, and physical capacity, in patients with knee OA. Sixty-two female volunteers with a diagnosis of knee OA were distributed in 4 groups: exercise associated with placebo PBM group, exercise associated with active PBM group, active PBM group, and placebo PBM group. Sixteen sessions of lower limb strength exercises and PBM via cluster (808 nm, 100 mW, 7 points each side, 56 J total) were performed. The level of pain, physical capacity, and lower limb muscle strength were evaluated with the use of the numeric pain rating scale (NPRS), 6-min walking test (6-MWT) and timed up and go (TUG), and maximal voluntary isometric torque (MVIT) before and after the interventions. Both groups presented a significant decrease in the level of pain when compared with the placebo-treated women. Furthermore, the 6-MWT showed that the trained groups (with or without PBM) demonstrated higher values in the distance walked comparing pre and post-treatment values. The same behavior was found for the MVIT load before and after intervention. TUG was higher for all the treated with exercise groups comparing the pre and post-treatment values. Physical exercise and PBM showed analgesic effects. However, PBM did not have any extra effect along with the effects of exercise in improving the distance walked, the TUG, and the muscle strength.Trial registration: RBR-7t6nzr.

Ultrasound plus low-level laser therapy for knee osteoarthritis rehabilitation: a randomized, placebo-controlled trial.

This study evaluated the synergistic effects of ultrasound (US) and low-level laser therapy (LLLT) with or without therapeutic exercises (TE) in women with knee osteoarthritis. Forty-two Caucasian women with knee osteoarthritis were allocated into three groups: (1) the placebo group who did not perform TE, but the prototype without emitting light or ultrasonic waves was applied, (2) the US + LLLT group in which only the prototype was applied and (3) the TE + US + LLLT group that performed TE before the prototype was applied. However, 35 women completed the full clinical trial. Pressure pain thresholds (PPT) using an algometer and functional performance during the sit-to-stand test were carried out. The average PPT levels increased for US + LLLT (41 ± 9 to 54 ± 15 N, p < 0.01) and TE + US + LLLT (32 ± 8 to 45 ± 9 N, p < 0.01) groups. The number of sit-to-stands was significantly higher for all groups. However, the change between pre-treatment and post-treatment (delta value) was greater for the US + LLLT (4 ± 1) and TE + US + LLLT groups (5 ± 1) than for the placebo group (2 ± 1) with a significant intergroup difference (p < 0.05). This study showed reduced pain and increased physical functionality after 3 months of US + LLLT with and without TE.

Long-term results of a randomized, controlled, double-blind study of low-level laser therapy before exercises in knee osteoarthritis: laser and exercises in knee osteoarthritis.

OBJECTIVES: To assess the long-term effects of low-level laser therapy (LLLT), in combination with strengthening exercises in patients with osteoarthritis of the knee. DESIGN: Follow-up results at three and six months in a previously published randomized, double-blind, placebo-controlled trial. SETTING: Specialist Rehabilitation Services. SUBJECTS: Forty participants of both genders, aged 50-75 years with knee osteoarthritis grade 2-4 on Kellgren-Lawrence scale. INTERVENTION: The LLLT group received 10 LLLT treatments with invisible infrared laser (904 nm, 3 Joules/point) over three weeks followed by an eight-week supervised strengthening exercise program. The placebo LLLT group received identical treatment, but the infrared laser output was disabled. MAIN MEASURES: Pain on a visual analogue scale, paracetamol consumption, and osteoarthritis severity measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne Index. RESULTS: The new data obtained during the follow-up period showed that all outcomes remained stable and there were no significant differences between the groups at three and six months. However, daily consumption of rescue analgesics (paracetamol) was significantly lower in the LLLT group throughout the follow-up period, ending at a group difference of 0.45 vs. 3.40 units ( P < 0.001) at six months follow-up. We conclude that within the limitations of this small study, the previously reported improvement after LLLT plus exercise was maintained for a period of six months. CONCLUSION: We find that the immediate post-intervention improvements from LLLT plus strengthening exercises were maintained for six months.

Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation.

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-1ß, 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-1ß, 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-1ß 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.

¹5³Sm-HM for arthritic knee pain. Estimated dosimetry.

Osteoarthritis is the most common type of arthropathy and after cardiovascular diseases is the most disabling disease in developing countries. The dosimetry for the clinical application of 153-samarium-hydroxymacroaggregates (¹5³Sm-HM) for radiation synovectomy (RSV) and palliative treatment for arthritic pain, as far as we know, has not been reported. The aim of this research was to estimate the radiation dose necessary for synovial ablation and pain palliation with minimum risk to the patient. ¹5³Sm-HM (370 MBq) was administered intra-articularly in a patient with severe knee pain and hindered motility. Regions of interest drawn on sequential, conjugated, anterior and posterior scintigraphy images were used to obtain the respective activity. The data was entered into a knee joint histological-geometric model designed with micrometric dimensions to represent the synovial cell layers. The Monte Carlo code was used to calculate the absorbed dose in each of the 12 model-cells representing the distance from the synovial liquid to the cartilage or bone. The absorbed dose in the synovial cavity was 114 Gy which is sufficient energy for RSV. The treated patient referred little pain and higher motility with no adverse reactions. ¹5³Sm-HM is a potentially valid radiopharmaceutical for RSV, which effectively palliates knee pain.