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Tel: (416) 251 -1005 Toll Free: (888) 557 -4004 Meditech International Inc. info@bioflexlaser. com www. bioflexlaser. com 415 Horner Avenue, Toronto, Ontario M 8 W 4 W 3 Low Intensity Laser Therapy Science and Clinical Applications Slava Kim, MD Clinic Director Copyright © 2008 Meditech International Incorporated. ALL RIGHTS RESERVED.

Lasers – What comes to mind?

Sun Gods Temple of Apollo Greek Sun God Ra Egyptian Sun God Belenus Celtic Sun God

Healing with light is a common concept in many cultures

Light as a healing force

Heliotherapy – Sunlight Therapy University of Virginia Medical Center Charlotteville, Virginia Circa 1929 Samuel and Nettie Bowne Hospital Poughkeepsie, New York. Circa 1935

Absence of Light on Human Body - SAD Seasonal Affective Disorder (SAD) – Bright Light Phototherapy has been shown to effectively treat seasonal affective disorder (SAD). – Non thermal and does not require specialized cells

Endre Mester - The Father of Laser Therapy May 29, 1966 • Endre Mester working at Semmelweiss hospital in Budapest, Hungary publishes the first paper on the stimulatory effects of ruby laser light on the skin of rats

Biological Photoacceptor Molecules Plants – Chlorophyll – Carotenoids Humans – – Rhodopsin (vision) Hemoglobin (blood) Myoglobin (muscle) Cytochrome (all cells)

The Electromagnetic Spectrum Decrease in wavelength = Increase in energy in a smaller area

Damage with Electromagnetic Radiation Two ways to cause damage 1. Ionizing radiation • Able to break bonds (i. e. DNA causing mutations) 2. Intensity • Thermal heating of tissue (i. e. microwave heating food)

Wavelengths in the Bio. Flex Systems • Red light at 660 nm • Infrared light at 840 nm and 830 nm

Cytochrome C Oxidase Absorption M. Cope thesis data modified by M. Patterson Red light at 660 nm and Infrared light at 830/840 nm

Published Absorption Spectra Desmet et. al. , Photomed. Laser Surg. 24(2): 121 -128, 2006 Red light at 660 nm and Infrared light at

Published Action Spectra Cu. A red 620 nm Cu. B oxid 680 nm Cu. B red 760 nm Cu. A oxid 820 nm Karu and Afanasyeva, DAN 392(5): 693, 1995 Wavelength, nm Red light at 660 nm and Infrared light at 830/840 nm

Biological Treatment Window M. Cope thesis data modified by M. Patterson Treatment Window

Laser Therapy Dosage - Arndt-Shultz Law Physiological Activity C A B Contr ol D Strength of Stimuli A. No light gives no effect B. Small amount of light also has no effect C. Maximal effect at the apex of the curve D. Inhibitory amount of light inhibits healing

Energy Production - Components NADH Dehydrogena Cytochrome se bc 1 Complex ATP Synthase Cytochrome c Oxidase

Electron Transport Chain H + H+ H+ H H + + H+ ADP ATP

Effect of Red and Infrared Light H+ H+ H + H+ H + ADP ATP

Laser Therapy Effects Put title of slide here Primary – The light is absorbed by cytochrome c oxidase Secondary – Release of NO into endothelium of blood vessels – Small increases in free radicals – Increased proton gradient in mitochondria Clinical – Wound Healing, Acceleration of the Inflammatory Process and Pain Influence

Published Effects of Light on Cells • Increased ATP production • Circulation – Relaxation of smooth muscles surrounding blood vessels – Angiogenesis • Increased production of: – Fibroblasts – Macrophage – Collagen • Altered nerve conduction • Increased metabolism of: – Endorphins – Acetylcholine – Serotonin • Increased synthesis of: – DNA – Proteins • Stimulation of immune response

Advantages of Laser Therapy • Non-toxic • Non allergic • Non invasive • Ease of application • No side effects • No complications • Completely safe • Cost effective • Superior alternative to: – analgesics – NSAID’s – other medications • Surgery may not be required

Conditions Treated I • Acute injuries/trauma – muscle tears/hematoma – tendon tears – ligament strain/sprains – fractures – subluxations – sport injuries • Musculoskeletal – repetitive stress injuries – rotator cuff tears – carpal tunnel syndrome – reflex sympathetic dystrophy – fibromyalgia – tempero-mandibular joint pathologies

Conditions Treated II • Inflammatory conditions – tendonitis – bursitis – myositis – fasciitis – synovitis – rheumatoid arthritis Autoimmune disease • Degenerative disorders – osteoarthritis – discogenic and vertebrogenic radiculopathies – calcifications • e. g. bone spurs – chondromalacia patella

Conditions Treated III • Other areas • Wound management – dermatological – ulcers • venous stasis – plastic surgery • diabetic – dental (e. g. gingivitis) • contact – gynecological • cervical pathologies – Podiatry • plantar fasciitis • biomechanical problems • atherosclerotic • Veterinary – equine – companion animals

Pain Mechanisms Pathways for pain relief by Red or Infrared laser therapy Local photoradiation effects occurring in less than 24 hrs Effects on biochemical inflammatory pathway Reduced PGE Levels (5) Reduced TNF Levels (2) Reduced IL 1 Levels (3) Reduced COX-2 expression (2) Reduced Plasminogen activator Levels (3) Effects on cells and soft tissue Reduced Edema formation (7) Reduced Hemorrhagic formation (2) Reduced Neutrophil cell influx (4) Reduced Cell apoptosis (3) Improved Microcirculation (4)

Inflammation Acute Phase Plasma derived mediators - Bradykinin - complement (C 3, C 5 a, MAC) - coagulation (Factor XII, Plasmin, Thrombin) Cell derived mediators Preformed: Lysosome granules - vasoactive amines (Histamine, Serotonin) Synthesized on demand: - cytokines (IFN-γ, IL-8, TNF-α, IL-1) - eicosanoids (Leukotriene B 4, Prostaglandins) - Nitric oxide - Kinins Chronic Phase Macrophage - Epithelioid cell - Giant cell - Granuloma

Key Effects that Apply to Diabetes Primary Effects • ATP production and Membrane permeability > Accelerated Metabolism Secondary Effects Clinical Effects • Nitric Oxide Stimulation > Angiogenesis • Endothelial Growth Factor > Angiogenesis • Endorphin Release > Pain Reduction • Elevated Immune Response > Wound Healing • Increased Cell Metabolism > Acc. Inflammation Resp. e. g. Fibroblast activity > Increased collagen production

Evaluation of the degree of effectiveness of low level light therapy on the treatment of skin ulcers and delayed postoperative wound healing. Iusim M, Kimchy J, Pillar T, Mendes DG. Center for Implant Surgery, Flieman Geriatric Rehabilitation Hospital, Technion, Haifa, Israel. Orthopedics. 1992 Sep; 15(9): 1023 -6. Twenty-one patients with 31 postoperative delayed open wounds resistant to conventional therapy were randomly allocated to three groups. Group 1 was treated with red low level narrow band (LLNB) light (660 nm); Group 2 was treated with infrared LLNB light (940 nm); Group 3 was treated with a placebo such as the Biobeam machine (no light irradiation). Group 1 showed a significant improvement compared to groups 2 and 3 (t-test).

Systemic effects of low-intensity laser irradiation on skin microcirculation in patients with diabetic microangiopathy. Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation. We demonstrate low-intensity laser irradiation on skin blood circulation in patients with diabetic microangiopathy. Patients are randomized; A) single helium-neon (He. Ne, 632. 8 nm) lowintensity laser irradiation with a dose of 30 J/cm(2) or B) sham irradiation over the forefoot region in a double-blind, placebo-controlled clinical study. Skin blood circulation by means of temperature recordings over forefoot regions was detected by infrared thermography. A single dose of low-intensity laser irradiation = a rise in skin temperature. The placebo group = a drop in skin temperature occurred. Our data show a significant increase in skin circulation due to athermic laser irradiation in patients with diabetic microangiopathy and point to the possibility of inducing systemic effects.

Healing of Bone Affections and Gangrene with Low Intensity Laser Irradiation in Diabetic Patients Suffering from Foot Infections. Schindl M, Schindl A, Polzleitner D, Schindl L. Forsch Komplementarmed. 1998; 5(5): 244 -247. OBJECTIVE: Evaluation of low-intensity laser irradiation on the healing of bone affections and gangrene in patients suffering from diabetic microangiopathy. PATIENTS: Two consecutive diabetic male patients with gangrene, Osteomielitis, and bone fractures. INTERVENTION: Helium-neon laser irradiation (36 J/cm 2 ) 50 min/day. MAIN OUTCOME PARAMETER: Healing of gangrene and corticalis lesion as well as remineralisation of bone affections. RESULTS: Within a mean period of 14 weeks not only a complete healing of the diabetic gangrenes but also a radiographically determined reestablishment of corticalis and remineralisation of preexisting bone affections could be achieved. CONCLUSION: low-intensity laser irradiation should be further tested as an additional beneficial therapeutic modality for the healing of gangrene and bone affections in diabetic patients.

Diabetes Mellitus: infected dermal ulcers Interim progress Healing progressing Initial: Diabetic with 3 week old ulcer, previously surgically debrided. The ulcer was deep, painful and prior to treatment, resistant to surgical and antibiotic therapy. Final photo: Total healing achieved Patient, asymptomatic and discharged 10 treatments over 3 weeks

Diabetes Mellitus: Gangrenous Leg Dermal Ulcers Initial After 6 1 hour treatments

Diabetes Mellitus: Initial

Final, after 35 treatments

Diabetes Mellitus: Amputated III toe

Diabetes Mellitus Pre-Gangrenous Right Foot Initial

Intermediate

Intermediate

Final

Hemochromatosis Dermal Ulcers – 2 Years Initial

After 1 Treatment

After 5 Treatments

After 23 Treatments

After 36 Treatments

Final

1 -Year Follow-up

Study: Achilles Tendons Laser photostimulation of collagen production in healing rabbit Achilles tendons. Reddy GK, Stehno-Bittel L, Enwemeka CS. Following tenotomy and repair, the surgical hind limbs of the rabbits were immobilized in customized polyurethane casts. The experimental animals were treated with a 632. 8 nm He. Ne laser daily at 1. 0 J cm(-2) for 14 days. Results: Biochemical analyses of the tendons revealed a 26% increase in collagen concentration with laser photostimulation indicating a more rapid healing process in treated tendons compared to controls. Page 18

Left Achilles Tendonitis 10 treatments over 2 months Tenderness, Edema and partial loss of flexion 100% function, asymptomatic Initial 1 Month after final treatment

Inflammation – Achilles Tendonitis • LLLT at a dose of 5. 4 J per point can reduce inflammation (PGE 2) and pain in activated Achilles tendinitis. Bjordal et al. Br J Sports Med. 40(1): 76 -80, 2006. • Low-level laser therapy accelerates clinical recovery from chronic Achilles tendinopathy when added to an Eccentric Exercise regimen. For the LLLT group, the results at 4 weeks were similar to the placebo LLLT group results after 12 weeks. Stergioulas et al. American J. Sports Med. 36(5): 881, 2008.

Muscle Tear/Hematoma 3 treatments over 5 days

Hamstring Tear/Hematoma 4 treatments over 7 days

Post-Traumatic Hematoma Initial After 4 Treatments After 5 Treatments

Lateral Epicondylitis (tennis elbow) • A systematic review with procedural assessments and meta -analysis of low level laser therapy in lateral elbow tendinopathy was recently performed because other reviews had found laser therapy to be ineffective. • LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions, seem to offer short-term pain relief and less disability in LET, both alone and in conjunction with an exercise regimen. Bjordal et. al. BMC Musculoskelet Disord. 29(9): 75. 2008

Subacromial Impingement Syndrome • A meta-analysis of the literature in Subacromial Impingement Syndrome (SAIS) found that laser therapy is an effective single intervention when compared with placebo treatments, but adding laser treatment to therapeutic exercise did not improve treatment efficacy. • The overall results of this meta analysis found that exercise, joint mobilization, and laser therapy are effective physical interventions for decreasing pain and functional loss or disability for patients with SAIS. The current evidence does not support the use of ultrasound. Sauers. J Athletic Training. 40(3): 221 -223, 2005.

Muscle Fatigue • Recently published study was aimed to investigate the effect of low-level laser therapy (LLLT) (830 nm wavelength, 100 m. W output, spot size 0. 0028 cm(2), 200 s total irradiation time) on skeletal muscle fatigue. • Concluded that 830 nm LLLT can delay the onset of skeletal muscle fatigue in high-intensity exercises, in spite of increased blood lactate levels. Leal Junior et. al. Lasers Med Sci. Jul 23, 2008.

Joint Disorders • A systematic review on the effects of laser therapy in chronic joint disorders found “Low level laser therapy with the suggested dose range significantly reduces pain and improves health status in chronic joint disorders. ” Bjordal et al. Aust J Physio. 49: 107 -116, 2003.

Osteoarthritis • Efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomized placebo-controlled trials. • LLLT administered with optimal doses in an intensive 2 -4 week treatment regimen, seem to offer clinically relevant short-term pain relief for osteoarthritis of the knee. Bjordal et. al. BMC Musculoskelet Disord. 22(8): 51, 2007.

Thermal Burn (Heat) 5 Treatments Over 8 Days

Thermal Burn (Heat) 19 treatments over 2 months

Burns LLLT of deep second-degree cutaneous burns significantly increased the number of intact mast cells during the inflammatory and proliferative phases of healing, and decreased the total number of mast cells during the remodeling phase. Kaviani et. al. Lasers in Med. Sci. 21: 90, 2006. • A small pilot study used 400 m. W laser at 670 nm laser twice a week over 8 weeks on 19 patients with burn scars who were requesting laser therapy • Seventeen out of 19 lesions showed macroscopic improvement after the treatment (expressed in points on the Vancouver Scale) with no scars becoming worse Gaida et. al. Burns. 30: 362, 2004.

Fracture. R-Humerus. Age: 66/M Initial Intermediate Final 10/29/2006 11/04/2006 11/29/2006 11/01/2006 12/06/2006 10/25/2006

Bone Healing • A study performed in human osteoblast cells found “lowlevel laser therapy has a biostimulatory effect on human osteoblast-like cells during the first 72 h after irradiation. ” Stein et. al. Wien Klin Wochenschr. 120(3 -4): 112 -117, 2008. • The results of a study carried out in laboratory mice indicates “that the use of low-intensity laser promotes better repair of bone injury”. De Souza Merli et. al. Photomed Laser Surg. 23(2): 212 -215, 2005. • A more recent study in rabbits found that LILT “may accelerate the process of fracture repair or cause increases in callus volume and BMD, especially in the early stages of absorbing the hematoma and bone remodeling” Liu et. al. Photomed Laser Surg. 25(6): 487 -494, 2007.

Pain Laser therapy in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. • The goal of the study was to review the biological and clinical short-term effects of laser therapy in acute pain from soft-tissue injury. • Laser therapy can modulate inflammatory processes in a dose-dependent manner and can be titrated to significantly reduce acute inflammatory pain in clinical settings. Bjordal et al. Photomed Laser Surg. 24(2): 158 -168. 2006

Case Study: Pain Reduction Low level laser therapy with trigger points technique: A clinical study on 243 patients. (He. Ne 632. 8 nm visible red or infrared 820 -830 nm continuous wave and 904 nm pulsed emission. There are very promising "trigger points" (TPs), i. e. , myofascial zones of particular sensibility and of highest projection of focal pain points, due to ischemic conditions. Headaches and facial pain, skeletomuscular ailments, myogenic neck pain, shoulder and arm pain, epicondylitis humery, tenosynovitis, low back and radicular pain, Achilles tendinitis) to whom the "trigger points" Results: rigidity decreases, the mobility is restored (functional recovery), and the spontaneous or induced pain decreases or even disappears, by movement, too. LLLT improves local microcirculation and it can also improve oxygen supply to hypoxic cells in the TP areas and at the same time it can remove the collected waste products. Results measured according to VAS/VRS/PTM: in acute pain, diminished more than 70%; in chronic pain more than 60%. Clinical effectiveness (success or failure) depends on the correctly applied energy dose--over/underdosage produces opposite, negative effects on cellular metabolism. The use of analgesic drugs could be reduced or completely excluded. LLLT suggests that the laser beam can be used as monotherapy for pain treatment. Page 29

Pain Reduction - Mechanism • 830 nm laser irradiation induces varicosity formation, reduces mitochondrial membrane potential and blocks fast axonal flow in small and medium diameter rat dorsal root ganglion neurons: implications for the analgesic effects of laser. • Laser-induced neural blockade is suggested as a primary candidate for the mechanism of laser-induced pain relief. Chow et al. J Peripher Nerv Syst. 12(1): 28 -39, 2007.

Peripheral-Arterial Occlusive Disease (Frostbite 1992) – 86 yr. old podiatrist Initial After 5 Consecutive Days of Treatment 11/29/2006 Acute for 6 months

Buergers Disease. Thromboangitis Obliterans Initial: Final photo: June 11, color normal, one ulcer totally healed, 2 nd ulcer almost healed, foot warm to the touch, ready for weight bearing. Interim (4 -5) 12 treatments over 3 weeks 2 days after initiating treatments, foot no longer in jeopardy. Improved arterial circulation and venous filling.

Venous Stasis Dermal Ulceration 5 Treatments Over 9 Days

Chronic Lymphedema After 10 Treatments • • • Cyanosis and induration gone Good venous filling Mid-calf diameter same as left

Neck Pain • A randomized, double-blind, placebo-controlled study of low-level laser therapy (LLLT) in 90 subjects with chronic neck pain was conducted with the aim of determining the efficacy of 300 m. W, 830 nm laser in the management of chronic neck pain. • Low-level laser therapy (LLLT), at the parameters used in this study, was efficacious in providing pain relief for patients with chronic neck pain over a period of 3 months. Chow et al. Pain. 124: 201 -210, 2006

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