Efficacy of low-level laser therapy in patients with lower extremity tendinopathy or plantar fasciitis: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: We investigated the effectiveness of low-level laser therapy (LLLT) in lower extremity tendinopathy and plantar fasciitis on patient-reported pain and disability. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eligible articles in any language were identified through PubMed, Embase and Physiotherapy Evidence Database (PEDro) on the 20 August 2020, references, citations and experts. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: Only randomised controlled trials involving participants with lower extremity tendinopathy or plantar fasciitis treated with LLLT were included. DATA EXTRACTION AND SYNTHESIS: Random effects meta-analyses with dose subgroups based on the World Association for Laser Therapy treatment recommendations were conducted. Risk of bias was assessed with the PEDro scale. RESULTS: LLLT was compared with placebo (10 trials), other interventions (5 trials) and as an add-on intervention (3 trials). The study quality was moderate to high.Overall, pain was significantly reduced by LLLT at completed therapy (13.15 mm Visual Analogue Scale (VAS; 95% CI 7.82 to 18.48)) and 4-12 weeks later (12.56 mm VAS (95% CI 5.69 to 19.42)). Overall, disability was significantly reduced by LLLT at completed therapy (Standardised Mean Difference (SMD)=0.39 (95% CI 0.09 to 0.7) and 4-9 weeks later (SMD=0.32 (95% CI 0.05 to 0.59)). Compared with placebo control, the recommended doses significantly reduced pain at completed therapy (14.98 mm VAS (95% CI 3.74 to 26.22)) and 4-8 weeks later (14.00 mm VAS (95% CI 2.81 to 25.19)). The recommended doses significantly reduced pain as an add-on to exercise therapy versus exercise therapy alone at completed therapy (18.15 mm VAS (95% CI 10.55 to 25.76)) and 4-9 weeks later (15.90 mm VAS (95% CI 2.3 to 29.51)). No adverse events were reported. CONCLUSION: LLLT significantly reduces pain and disability in lower extremity tendinopathy and plantar fasciitis in the short and medium term. Long-term data were not available. Some uncertainty about the effect size remains due to wide CIs and lack of large trials. PROSPERO REGISTRATION NUMBER: CRD42017077511.

Short- and Long-Term Effectiveness of Low-Level Laser Therapy Combined with Strength Training in Knee Osteoarthritis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Both physical activity and low-level laser therapy (LLLT) can reduce knee osteoarthritis (KOA) inflammation. We conducted a randomized clinical trial to investigate the short- and long-term effectiveness of LLLT combined with strength training in persons with KOA. METHODS: Fifty participants were randomly divided in two groups, one with LLLT plus strength training (n = 26) and one with placebo LLLT plus strength training (n = 24). LLLT and strength training were performed triweekly for 3 and 8 weeks, respectively. In the laser group, 3 joules 904 nm wavelength laser was applied to fifteen points (45 joules) per knee per session. Patient-reported outcomes, physical tests, and ultrasonography assessments were performed at baseline and 3, 8, 26, and 52 weeks after initial LLLT or placebo therapy. The primary outcomes were pain on movement, at rest, at night (Visual Analogue Scale), and globally (Knee injury and Osteoarthritis Outcome Score (KOOS) subscale). Parametric data were assessed with analysis of variance using Sidák's correction. RESULTS: There were no significant between-group differences in the primary outcomes. However, in the laser group there was a significantly reduced number of participants using analgesic and non-steroidal anti-inflammatory drugs and increased performance in the sit-to-stand test versus placebo-control at week 52. The joint line pain pressure threshold (PPT) improved more in the placebo group than in the laser group, but only significantly at week 8. No other significant treatment effects were present. However, pain on movement and joint line PPT were worse in the placebo group at baseline, and therefore, it had more room for improvement. The short-term percentage of improvement in the placebo group was much higher than in similar trials. CONCLUSIONS: Pain was reduced substantially in both groups. LLLT seemed to provide a positive add-on effect in the follow-up period in terms of reduced pain medication usage and increased performance in the sit-to-stand test.

Pain and Disability of Conservatively Treated Distal Radius Fracture: A Triple-Blinded Randomized Placebo-Controlled Trial of Photobiomodulation Therapy.

Objective: Many patients with distal radius fracture (DRF) experience pain and disability after removal of the cast. The aim of this study was to investigate if photobiomodulation therapy (PBMT) applied after cast removal provides an add-on effect to a home-based exercise program in rehabilitation after DRF. Methods: In this triple-blinded placebo-controlled trial, 50 patients with conservatively treated DRF were randomized to receive either active PBMT or placebo PBMT after cast removal in addition to a home-based exercise therapy program. The outcome measures were the Patient-Rated Wrist and Hand Evaluation (PRWHE) questionnaire, night pain (NP), and consumption of analgesic medication (AM) and were evaluated after cast removal at 4 (baseline), 8, 12, and 26 weeks after injury. NP and AM were also evaluated 7 weeks after injury (end of active/placebo PBMT). Results: There was a significant between-group difference in PRWHE scores in favor of active PBMT 8, 12, and 26 weeks after DRF. NP and consumption of AM were significantly lower in the active PBMT group from 7 to 26 weeks. There was a minimum clinically important improvement between the groups in favor of active PBMT in total score at 12 weeks, in pain subscore at 8, 12, and 26 weeks, and in disability subscore at 8 and 12 weeks. Conclusions: PBMT is safe and has long-term positive effect on pain and disability in DRF patients, when applied in combination with a home-based rehabilitation exercise program. Clinical Trial registration number: NCT03014024.

Efficacy of mobilisation with movement in chronic shoulder pain: protocol for a systematic review and meta-analysis of controlled trials.

INTRODUCTION: Shoulder pain affects approximately one in four adults and is thus one of the most common musculoskeletal problems. Only 50% of patients who begin treatment for shoulder pain are cured within 6 months. There is a need for systematic reviews to estimate the effectiveness of shoulder treatments. We decided to evaluate the effect of mobilisation with movement (MWM) on chronic shoulder pain in a systematic review. METHODS AND ANALYSIS: The review will include controlled trial articles identified via five electronic databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and Cochrane Central Register of Controlled Trials), reference lists, citations searches and experts in the field. Only controlled trials involving participants with a mean duration of pain of ≥3 months, in which the effectiveness of MWM has been compared with non-invasive treatments, sham mobilisation or wait-and-see will be included. The included trials will be synthesised with random effects meta-analyses. Risk-of-bias will be assessed with the Physiotherapy Evidence Database 0-10 point scale. ETHICS AND DISSEMINATION: The review does not require ethics approval as it is based on anonymised data from trial reports. The results of the review will be disseminated through a peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42018109380.

Effectiveness of Low-Level Laser Therapy Associated with Strength Training in Knee Osteoarthritis: Protocol for a Randomized Placebo-Controlled Trial.

Physical activity and low-level laser therapy (LLLT) can reduce knee osteoarthritis (KOA) inflammation. We are conducting a randomized placebo-controlled trial to investigate the long-term effectiveness of LLLT combined with strength training (ST) in persons with KOA, since it, to our knowledge, has not been investigated before. Fifty participants were enrolled. LLLT and ST was performed 3 times per week over 3 and 8 weeks, respectively. In the LLLT group, 3 Joules of 904 nm wavelength laser was applied to 15 spots per knee (45 Joules/knee/session). The primary outcomes are pain during movement, at night and at rest (Visual Analogue Scale) and global pain (Knee injury and Osteoarthritis Outcome Score, KOOS) pain subscale. The secondary outcomes are KOOS disability and quality-of-life, analgesic usage, global health change, knee active range of motion, 30 s chair stand, maximum painless isometric knee extension strength, knee pain pressure threshold and real-time ultrasonography-assessed suprapatellar effusion, meniscal neovascularization and femur cartilage thickness. All the outcomes are assessed 0, 3, 8, 26 and 52 weeks post-randomization, except for global health change, which is only evaluated at completed ST. This study features the blinding of participants, assessors and therapists, and will improve our understanding of what occurs with the local pathophysiology, tissue morphology and clinical status of persons with KOA up to a year after the initiation of ST and a higher 904 nm LLLT dose than in any published trial on this topic.

Treatment of Distal Radius Fracture During Immobilization with an Orthopedic Cast: A Double-Blinded Randomized Controlled Trial of Photobiomodulation Therapy.

Objective: With distal radius fracture (DRF) many patients experience stiffness and pain after removal of the cast. The aim of this study was to investigate possible effects of photobiomodulation therapy (PBMT) in DRF during immobilization with semicircular orthopedic cast. Methods: In this double-blinded, placebo-controlled trial, 53 patients with DRF were randomized to receive nine treatments of either PBMT or placebo-PBMT. The fractures were irradiated through openings in the cast. Patient-Rated Wrist and Hand Evaluation (PRWHE) questionnaire and clinical outcomes were measured at baseline, 4, 8, 12, and 26 weeks after the trauma. Results: No significant differences were found for PRWHE scores, although PBMT was significantly superior to placebo regarding active range of motion [AROM; 95% (confidence interval) CI: -65.25° to -20.42° and -25.57° to -0.73°, respectively] and grip strength at week 4 (95% CI: -12.10 to -1.67 kg). Side-to-side differences between injured and noninjured wrists were significantly smaller in the PBMT group regarding grip and pinch strength at week 4 (95% CI: 0.89 to 8.87 kg and 0.55 to 3.79 kg, respectively). Significantly less patients in the PBMT group reported night pain at week 3. Conclusions: PBMT administered during the immobilization period of DRF had no effect on perceived pain and function measured through PRWHE. Night pain was significantly reduced after 3 weeks by PBMT. PBMT significantly improved pinch and grip strength and AROM, but these findings did not translate to the subjective experience of pain and function. Trial registration number: Clinical.trials.gov number NCT02749929. The study was approved by the Regional ethics committee (REK-Vest) in Norway (App. No: 2015/330). Informed consent was obtained from all patients.

Photobiomodulation Therapy is Able to Modulate PGE2 Levels in Patients With Chronic Non-Specific Low Back Pain: A Randomized Placebo-Controlled Trial.

BACKGROUND AND OBJECTIVES: Non-specific low back pain (LBP) is responsible for triggering increased biomarkers levels. In this way, photobiomodulation therapy (PBMT) may be an interesting alternative to treat these patients. One of the possible biological mechanisms of PBMT involved to decrease pain intensity in patients with musculoskeletal disorders is modulation of the inflammatory mediators' levels. The aim of this study was to evaluate the effects of PBMT compared with placebo on inflammatory mediators' levels and pain intensity in patients with chronic non-specific LBP. STUDY DESIGN/MATERIALS AND METHODS: A prospectively registered, randomized triple-blinded (volunteers, therapists, and assessors), placebo-controlled trial was performed. Eighteen patients with chronic non-specific LBP were recruited and treated with a single session of active PBMT or placebo PBMT. The primary outcome of the study was serum prostaglandin E2 levels and the secondary outcomes were tumor necrosis factor-α, interleukin-6 levels, and pain intensity. All outcomes were measured before and after 15 minutes of treatment session. RESULTS: PBMT was able to decrease prostaglandin E2 levels at post-treatment compared with placebo, with a mean difference of -1470 pg/ml, 95% confidence interval -2906 to -33.67 in patients with LBP. There was no difference between groups in the other measured outcomes. Patients did not report any adverse events. CONCLUSION: Our results suggest that PBMT was able to modulate prostaglandin E2 levels, indicating that this may be one of the mechanisms involved in the analgesic effects of PBMT in patients with LBP. Trial registration number (ClinicalTrials.gov): NCT03859505. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

What is the optimal time-response window for the use of photobiomodulation therapy combined with static magnetic field (PBMT-sMF) for the improvement of exercise performance and recovery, and for how long the effects last? A randomized, triple-blinded, placebo-controlled trial.

BACKGROUND: The optimal time-response window for photobiomodulation therapy (PBMT) using low-level laser therapy (LLLT) and/or light emitting diodes therapy (LEDT) combined with static magnetic fields (sMF) before physical activity still was not fully investigated. The aim of the present study was to investigate the better of four time-response windows for PBMT combined with sMF (PBMT-sMF) use before exercise in humans. METHODS: A prospectively registered, randomized, triple-blinded (volunteers, therapists and assessors) placebo-controlled trial was carried out. Sixty healthy untrained male subjects were randomly allocated to six experimental groups (n = 10 per group): PBMT-sMF 5 mins, PBMT-sMF 3 h, PBMT-sMF 6 h, PBMT-sMF 1-day, placebo, and control. The control group performed all procedures, however did not receive any kind of intervention. PBMT-sMF active or PBMT-sMF placebo was applied precisely in different time points after baseline MVC test to ensure that both MVC tests and eccentric exercise protocol would occur at the same hour of the day in all groups. Then, after five minutes, 3 h, 6 h or 1-day (24 h) of PBMT-sMF treatment (active or placebo) the eccentric exercise protocol was performed. The primary outcome was peak torque obtained from maximum voluntary contraction (MVC). The secondary outcomes were creatine kinase (CK), and delayed onset muscle soreness (DOMS). The primary and secondary outcomes were measured at baseline, immediately after, 1 h, 24 h and 48 h after the eccentric exercise protocol. RESULTS: Sixty patients were randomized and analyzed to each sequence. The outcomes in absolute values show that all active PBMT-sMF groups increased (p < 0.05) MVC from immediately after to 1 h after eccentric exercise, and decreased (p < 0.05) CK activity at all time points. However, PBMT-sMF 5 mins, 3 h and 6 h groups showed better results in MVC and CK analysis from 24 h to 48 h, and also to DOMS (p < 0.05) at all time points. Participants did not report any adverse events. CONCLUSIONS: PBMT-sMF can be used from 5 min to 6 h before exercise, and the effects can last up to 54 h after treatment. However, the effects start to decrease when a 1-day (24 h) time-response window is used. TRIAL REGISTRATION: NCT03420391. Registered 05 February 2018.

Reliability of pain pressure threshold algometry in persons with conservatively managed wrist fractures.

OBJECTIVE: Wrist fracture is a common injury in Norway. Pressure algometry is widely used to quantify patients' pain threshold in various anatomical locations. The aim of this study was to explore the reliability of pain pressure threshold (PPT) algometry in persons with conservatively managed distal radius fractures. METHODS: In this cross-sectional study, three raters (A, B, and C) tested the PPT of participants (18-97 years of age) with a unilateral distal radius fracture after removal of the cast. The raters conducted two measurements of both wrists. Intrarater reliability was examined in 75, 50, and 25 participants by Raters A, B, and C, respectively. Interrater reliability was tested in 50 and 25 participants by Rater Pairs A-B and A-C, respectively. Relative reliability was calculated with intraclass correlation coefficient (ICC1.1 ) and absolute reliability using within-subject standard deviation (Sw ). RESULTS: There was a significant difference in the PPT between the participants' injured and noninjured wrists (p < .0001). The mean PPT was 29% lower in the injured than in the noninjured wrists, 175 kPa (SD ± 62) versus 248 kPa (SD ± 83). Intrarater reliability (A) of PPT algometry was better in injured wrists than in noninjured wrists (ICC1.1  = 0.825 vs. 0.765 and Sw  = 27 vs. 43 kPa). Similarly, interrater reliability of PPT algometry was better in injured wrists than in noninjured wrists. In injured wrists, the interrater reliability of PPT algometry between Raters A and B was 0.617 (ICC1.1 ) and Sw was 51 kPa, and between Raters A and C, the interrater reliability was 0.706 (ICC1.1 ) and Sw was 48 kPa. CONCLUSION: PPT algometry is a useful measurement tool with acceptable reliability and thus suitable for monitoring and quantifying pain in persons with conservatively managed wrist fractures. To be more certain that a change has occurred, the same rater should perform the measurements.

Efficacy of low-level laser therapy on pain and disability in knee osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials.

OBJECTIVES: Low-level laser therapy (LLLT) is not recommended in major knee osteoarthritis (KOA) treatment guidelines. We investigated whether a LLLT dose-response relationship exists in KOA. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eligible articles were identified through PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and Cochrane Central Register of Controlled Trials on 18 February 2019, reference lists, a book, citations and experts in the field. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We solely included randomised placebo-controlled trials involving participants with KOA according to the American College of Rheumatology and/or Kellgren/Lawrence criteria, in which LLLT was applied to participants' knee(s). There were no language restrictions. DATA EXTRACTION AND SYNTHESIS: The included trials were synthesised with random effects meta-analyses and subgrouped by dose using the World Association for Laser Therapy treatment recommendations. Cochrane's risk-of-bias tool was used. RESULTS: 22 trials (n=1063) were meta-analysed. Risk of bias was insignificant. Overall, pain was significantly reduced by LLLT compared with placebo at the end of therapy (14.23 mm Visual Analogue Scale (VAS; 95% CI 7.31 to 21.14)) and during follow-ups 1-12 weeks later (15.92 mm VAS (95% CI 6.47 to 25.37)). The subgroup analysis revealed that pain was significantly reduced by the recommended LLLT doses compared with placebo at the end of therapy (18.71 mm (95% CI 9.42 to 27.99)) and during follow-ups 2-12 weeks after the end of therapy (23.23 mm VAS (95% CI 10.60 to 35.86)). The pain reduction from the recommended LLLT doses peaked during follow-ups 2-4 weeks after the end of therapy (31.87 mm VAS significantly beyond placebo (95% CI 18.18 to 45.56)). Disability was also statistically significantly reduced by LLLT. No adverse events were reported. CONCLUSION: LLLT reduces pain and disability in KOA at 4-8 J with 785-860 nm wavelength and at 1-3 J with 904 nm wavelength per treatment spot. PROSPERO REGISTRATION NUMBER: CRD42016035587.

Effects of photobiomodulation therapy on inflammatory mediators in patients with chronic non-specific low back pain: Protocol for a randomized placebo-controlled trial.

INTRODUCTION: Low back pain (LBP) is ranked as one of the most prevalent health conditions. It is likely that some inflammatory mediators could be associated with pain and disability in these patients. Photobiomodulation therapy (PBMT) is a non-pharmacological therapy often used in patients with LBP and one of the possible mechanisms of action of therapy is modulate inflammatory mediators. However, to date there are no studies that evaluated the effects of PBMT on the levels of inflammatory mediators in patients with LBP. The aim of this study is to evaluate the acute effects of PBMT on systemic levels of inflammatory mediators and pain intensity in patients with chronic non-specific low back pain. METHODS AND ANALYSIS: This is a prospectively registered, two-arm randomized placebo-controlled trial with blinded patients, assessors and therapists. Eighteen patients with chronic non-specific LBP will be randomized into 2 groups: placebo or active PBMT. The treatment will be provided in a single session. The primary outcome will be levels of prostaglandin E2 (PGE2). The secondary outcomes will be levels of necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and pain intensity. Biochemical and clinical outcomes will be measured at baseline and 15 minutes after the single treatment session. DISCUSSION: Despite PBMT be used in musculoskeletal disorders such as LBP, to the best of our knowledge this is the first study that will investigate a possible biological mechanism behind the positive clinical effects of PBMT on non-specific chronic low back pain. ETHICS AND DISSEMINATION: The study was approved by the Regional Research Ethics Committee. The results will be disseminated through publication in peer-reviewed international journal and conferences. TRIAL REGISTRATION NUMBER: NCT03859505.

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.

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.

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

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

Achilles Tendon Penetration for Continuous 810 nm and Superpulsed 904 nm Lasers Before and After Ice Application: An In Situ Study on Healthy Young Adults.

BACKGROUND AND OBJECTIVE: There is a lack of knowledge about the influence tissue temperature may have on laser light penetration and tendon structure. The purpose of this study was to investigate whether penetration of laser energy in human Achilles tendons differed before and after ice pack application. MATERIALS AND METHODS: The Achilles tendons (n = 54) from 27 healthy young adults were irradiated with two class 3B lasers (810 nm 200 mW continuous mode laser and a 904 nm 60 mW superpulsed mode laser). The optical energy penetrating the Achilles area was measured before and after 20 min of ice application. Measurements were obtained after 30, 60, and 120 sec irradiation with the 904 nm laser and after 30 and 60 sec irradiation with the 810 nm laser. Achilles tendon thickness was measured with ultrasonography. RESULTS: Optical energy penetration increased significantly (p < 0.01) after ice application for both lasers and at all time points from 0.34% to 0.39% of energy before ice application to 0.43-0.52% of energy after ice application for the 904 nm laser and from 0.24% to 0.25% of energy before ice application to 0.30-0.31% of energy after ice application for the 810 nm laser. The energy loss per centimeter of irradiated tissue was significantly higher (p < 0.05) at all time points after ice application. Ultrasonography imaging of skin-to-skin and transversal tendon thickness was significantly reduced after ice application at p = 0.05 and p = 0.03, respectively. Achilles tendon thickness in the longitudinal plane remained unchanged (p = 0.49). CONCLUSIONS: The penetration of laser light increased significantly through healthy Achilles tendons subjected to 20 min of cooling. These findings occurred in the presence of a significant reduction in skin temperature and Achilles tendon thickness.

Penetration Time Profiles for Two Class 3B Lasers in In Situ Human Achilles at Rest and Stretched.

BACKGROUND AND OBJECTIVE: The majority of studies investigating penetration of laser light are performed in vitro on skin flaps, with measures of immediate penetration depth and energy loss. The aim of this study was to investigate the penetration time profiles for two different lasers used in low-level laser therapy, during 150 sec of exposure both in stretched and relaxed human Achilles in situ. MATERIALS AND METHODS: Thirty-four Achilles tendons from 17 healthy volunteers were irradiated by an 810 nm, 200 mW, continuous- and a 904 nm, 60 mW, super-pulsed laser. Irradiation was performed with the Achilles tendons in relaxed and stretched condition. The energy penetrating skin-skin was measured every 30 sec using an optical power meter. RESULTS: The 810 nm laser penetration ability did not differ significantly in relaxed and stretched condition with 0.17% [standard error of the mean (SEM) 0.02] of mean output power (MOP) and 0.02% (SEM 0.004) of MOP, respectively. The 904 nm laser demonstrated a statistical significant (p < 0.05) and almost linear increasing penetration ability both in relaxed and stretched Achilles from 0.25% (SEM 0.03) to 0.38% (SEM 0.04) of MOP and from 0.05% (SEM 0.01) to 0.13% (SEM 0.01) of MOP, respectively. The penetrated ability differed between lasers and tissue conditions at all measure points (p < 0.05). CONCLUSIONS: The 904 nm laser penetrates relatively more energy than the 810 nm laser in in situ human Achilles. Moreover, penetration from the super-pulsed 904 nm laser increased during exposure time, whereas penetration from the 810 nm laser was constant. In addition, stretching the Achilles causes a higher energy attenuation by the tissue.

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.

Evaluation of the Proliferative Effects Induced by Low-Level Laser Therapy in Bone Marrow Stem Cell Culture.

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).