Laser therapy dosage, penetration

Photobiomodulation, Photomedicine, and Laser Surgery Volume 37, Number 10, 2019 ª Mary Ann Liebert, Inc. Pp. 581–595 DOI: 10.1089/photob.2019.4676

Penetration Profiles of Visible and Near-Infrared Lasers and Light-Emitting Diode Light Through the Head Tissues in Animal and Human Species: A Review of Literature

Farzad Salehpour, MSc,1,2 Paolo Cassano, MD, PhD,3–5 Naser Rouhi, MSc,6 Michael R. Hamblin, PhD,7–9 Luis De Taboada, MSEE,10 Fereshteh Farajdokht, PhD,1 and Javad Mahmoudi, PhD1

Abstract

Background and objective: Photobiomodulation (PBM) therapy is a promising and noninvasive approach to stimulate neuronal function and improve brain repair. The optimization of PBM parameters is important to maximize effectiveness and tolerability. Several studies have reported on the penetration of visible-to-near-infrared (NIR) light through various animal and human tissues. Scientific findings on the penetration of PBM light vary, likely due to use of different irradiation parameters and to different characteristics of the subject such as species, age, and gender.

Materials and methods: In this article, we review published data on PBM penetration through the tissues of the head in both animal and human species. The patterns of visible-to-NIR light penetration are summarized based on the following study specifications: wavelength, coherence, operation mode, beam type and size, irradiation site, species, age, and gender.

Results: The average penetration of transcranial red/NIR (630–810 nm) light ranged 60–70% in C57BL/6 mouse (skull), 1–10% in BALB/c mouse (skull), 10–40% in Sprague–Dawley rats (scalp plus skull), 20% in Oryctolagus cuniculus rabbit (skull), 0.11% in pig (scalp plus skull), and 0.2–10% in humans (scalp plus skull). The observed variation in the reported values is due to the difference in factors (e.g., wavelengths, light coherence, tissue thickness, and anatomic irradiation site) used by researchers. It seems that these data challenge the applicability of the animal model data on transcranial PBM to humans. Nevertheless, two animal models seem particularly promising, as they approximate penetration in humans: (I) Penetration of 808 nm laser through the scalp plus skull was 0.11% in the pig head; (II) Penetration of 810 nm laser through intact skull was 1.75% in BALB/c mouse.

Conclusions: In conclusion, it is worthwhile mentioning that since the effectiveness of brain PBM is closely dependent on the amount of light energy reaching the target neurons, further quantitative estimation of light penetration depth should be performed to validate the current findings. Keywords: transcranial photobiomodulation, low-level laser (light) therapy, optical properties, penetration depth, brain tissues, skull


Photomedicine and Laser Surgery Volume 30, Number 12, 2012 ª Mary Ann Liebert, Inc. Pp. 688–694 DOI: 10.1089/pho.2012.3306

Skin Penetration Time-Profiles for Continuous 810 nm and Superpulsed 904 nm Lasers in a Rat Model

Jon Joensen, P.T., M.Sc.,1,2 Knut Øvsthus, MIng, Ph.D.,3 Rolf K. Reed, M.D., Ph.D.,4 Steinar Hummelsund, P.T., M.Sc.,1 Vegard V. Iversen, Phys., Ph.D.,5 Rodrigo A´ lvaro Branda˜ o Lopes-Martins, Ph.D.,6 and Jan Magnus Bjordal, P.T., Ph.D.1,2

Abstract

Objective: The purpose of this study was to investigate the rat skin penetration abilities of two commercially available low-level laser therapy (LLLT) devices during 150 sec of irradiation.

Background data: Effective LLLT irradiation typically lasts from 20 sec up to a few minutes, but the LLLT time-profiles for skin penetration of light energy have not yet been investigated. Materials and methods: Sixty-two skin flaps overlaying rat’s gastrocnemius muscles were harvested and immediately irradiated with LLLT devices. Irradiation was performed either with a 810 nm, 200 mW continuous wave laser, or with a 904 nm, 60 mW superpulsed laser, and the amount of penetrating light energy was measured by an optical power meter and registered at seven time points (range, 1–150 sec).

Results: With the continuous wave 810 nm laser probe in skin contact, the amount of penetrating light energy was stable at *20% (SEM – 0.6) of the initial optical output during 150 sec irradiation. However, irradiation with the superpulsed 904 nm, 60 mW laser showed a linear increase in penetrating energy from 38% (SEM – 1.4) to 58% (SEM – 3.5) during 150 sec of exposure. The skin penetration abilities were significantly different ( p < 0.01) between the two lasers at all measured time points.

Conclusions: LLLT irradiation through rat skin leaves sufficient subdermal light energy to influence pathological processes and tissue repair. The finding that superpulsed 904 nm LLLT light energy penetrates 2–3 easier through the rat skin barrier than 810 nm continuous wave LLLT, corresponds well with results of LLLT dose analyses in systematic reviews of LLLT in musculoskeletal disorders. This may explain why the differentiation between these laser types has been needed in the clinical dosage recommendations of World Association for Laser Therapy.


Photomedicine and Laser Surgery Volume 24, Number 6, 2006 © Mary Ann Liebert, Inc. Pp. 754–758 DOI: 10.1089/PHO.2006.2023

Comparative Study Using 685-nm and 830-nm Lasers in the Tissue Repair of Tenotomized Tendons in the Mouse

PATRICIA M. CARRINHO, M.S.,1 ANA CLAUDIA MUNIZ RENNO, Ph.D.,1 PAULO KOEKE, Ph.D.,1 ANA CLAUDIA BONOGNE SALATE, M.S.,1 NIVALDO ANTONIO PARIZOTTO, Ph.D.,1 and BENEDITO CAMPOS VIDAL, Ph.D.2

ABSTRACT

Objective: The objective of this study was to evaluate the effects of 685- and 830-nm laser irradiations, at different fluences on the healing process of Achilles tendon (Tendon calcaneo) of mice after tenotomy. Background Data: Some authors have shown that low-level laser therapy (LLLT) is able to accelerate the healing process of tendinuos tissue after an injury, increasing fibroblast cell proliferation and collagen synthesis. However, the mechanism by which LLLT acts on healing process is not fully understood.

Methods: Forty-eight male mice were divided into six experimental groups: group A, tenomized animals, treated with 685 nm laser, at the dosage of 3 J/cm2; group B, tenomized animals, treated with 685-nm laser, at the dosage of 10 J/cm2; group C, tenomized animals, treated with 830-nm laser, at dosage of 3 J/cm2; group D, tenomized animals, treated with 830-nm laser, at the dosage of 10 J/cm2; group E, injured control (placebo treatment); and group F, non-injured standard control. Animals were killed on day 13 post-tenotomy, and their tendons were surgically removed for a quantitative analysis using polarization microscopy, with the purpose of measuring collagen fibers organization trough the birefringence (optical retardation [OR]).

Results: All treated groups showed higher values of OR when compared to injured control group. The best organization and aggregation of the collagen bundles were shown by the animals of group A (685 nm, 3 J/cm2), followed by the animals of group C and B, and finally, the animals of group D.

Conclusion: All wavelengths and fluences used in this study were efficient at accelerating the healing process of Achilles tendon post-tenotomy, particularly after the 685-nm laser irradiation, at 3 J/cm2. It suggests the existence of wavelength tissue specificity and dose dependency. Further studies are required to investigate the physiological mechanisms responsible for the effects of laser on tendinuos repair.


Photomedicine and Laser Surgery Volume 32, Number 9, 2014 ª Mary Ann Liebert, Inc. Pp. 500–504 DOI: 10.1089/pho.2014.3745

Defining a Therapeutic Window for Laser Irradiation (810 nm) Applied to the Inguinal Region to Ameliorate Diabetes in Diabetic Mice

Philip V. Peplow, PhD,1 and G. David Baxter, DPhil2 Abstract Objective: The purpose of this study was to determine a therapeutic window of antidiabetic effect by laser irradiating the left inguinal region of diabetic mice (810 nm 20.4 and 40.8 J/cm2 ) for 7 days. Background data: Irradiation of 810 nm 10.2 J/cm2 to the left inguinal region of diabetic mice for 7 days significantly decreased blood plasma fructosamine compared with nonirradiated controls.

Methods: Forty-seven diabetic mice were used. Body weight and water intake of the mice were measured daily for 7 days prior to start of treatment (day 0). Mice were irradiated on the left inguinal region with 810 nm laser 20.4 J/cm2 (n = 15) or 40.8 J/cm2 (n = 15) for 7 days, or were not irradiated (control, n = 17). Body weight and water intake were measured to day 7. On day 7, mice were fasted for 5 h, anesthetized with sodium pentobarbitone (i.p.), and blood plasma was collected. The blood plasma was assayed for glucose and fructosamine.

Results: Water intake was significantly increased on day 7 compared with day 0 for diabetic mice receiving laser treatment. Blood plasma glucose levels on day 7 for diabetic mice irradiated 20.4 and 40.8 J/cm2 were not significantly different than for nonirradiated controls. The blood plasma fructosamine level of diabetic mice irradiated with 20.4 J/cm2 was significantly lower than for nonirradiated controls, whereas that for diabetic mice irradiated with 40.8 J/cm2 was not significantly different than for nonirradiated controls.

Conclusions: Irradiation (810 nm laser 10.2–20.4 J/cm2 ) to the left inguinal region of diabetic mice for 7 days has the potential to ameliorate diabetes, as is shown by decreased blood plasma fructosamine.


Photomedicine and Laser Surgery Volume 24, Number 1, 2006 © Mary Ann Liebert, Inc. Pp. 33–37

Low-Level Laser Therapy Induces Dose-Dependent Reduction of TNF Levels in Acute Inflammation

F. AIMBIRE,1 R. ALBERTINI,1 M.T.T. PACHECO,1 H.C. CASTRO-FARIA-NETO,2 P.S.L.M. LEONARDO,3 V.V. IVERSEN,5 R.A.B. LOPES-MARTINS, Ph.D.,3 and J.M. BJORDAL4

ABSTRACT

Objective: The aim of this study was to investigate if low-level laser therapy (LLLT) can modulate acute inflammation and tumor necrosis factor (TNF) levels. Background Data: Drug therapy with TNF-inhibitors has become standard treatment for rheumatoid arthritis, but it is unknown if LLLT can reduce or modulate TNF levels in inflammatory disorders.

Methods: Two controlled animal studies were undertaken, with 35 male Wistar rats randomly divided into five groups each. Rabbit antiserum to ovalbumin was instilled intrabronchially in one of the lobes, followed by the intravenous injection of 10 mg of ovalbumin in 0.5 mL to induce acute lung injury. The first study served to define the time profile of TNF activity for the first 4 h, while the second study compared three different LLLT doses to a control group and a chlorpromazine group at a timepoint where TNF activity was increased. The rats in LLLT groups were irradiated within 5 min at the site of injury by a 650-nm Ga-Al-As laser. Results: There was a time-lag before TNF activity increased after BSA injection. TNF levels increased from 6.9 (95% confidence interval [CI], 5.6–8.2) units/mL in the first 3 h to 62.1 (95% CI, 60.8–63.4) units/mL (p < 0.001) at 4 h. An LLLT dose of 0.11 Joules administered with a power density of 31.3 mW/cm2 in 42 sec significantly reduced TNF level to 50.2 (95% CI, 49.4–51.0), p < 0.01 units/mL versus control. Chlorpromazine reduced TNF level to 45.3 (95% CI, 44.0–46.6) units/mL, p < 0.001 versus control.

Conclusion: LLLT can reduce TNF expression after acute immunocomplex lung injury in rats, but LLLT dose appears to be critical for reducing TNF release


Photobiomodulation, Photomedicine, and Laser Surgery Volume XX, Number XX, 2020 ª Mary Ann Liebert, Inc. Pp. 1–6 DOI: 10.1089/photob.2019.4729

Biphasic Dose/Response of Photobiomodulation Therapy on Culture of Human Fibroblasts

Genoveva Lourdes Flores Luna, PhD,1 Ana Laura Martins de Andrade, PhD,2 Patricia Brassolatti, PhD,3 Paulo Se´ rgio Bossini, PhD,4 Fernanda de Freitas Anibal, PhD,3 Nivaldo Antonio Parizotto, PhD,2 and Aˆ ngela Merice de Oliveira Leal, PhD1

Abstract

Objective: The objective of this study was to evaluate the effects of application of different fluences and energies of laser in the 24-, 48-, and 72-h periods in fibroblasts originating from human skin (HFF-1). Methods: The cell used as a template for cell proliferation was HFF-1. For the photobiomodulation (PBM) application, a 660 nm laser with a power of 40 mW and energies of 0.84, 1.40, 5.88, and 6.72 J was used. Five experimental groups were studied: one control group (CG) with simulated PBM and four groups that received PBM in different doses. The changes observed after laser irradiation were evaluated by cell viability (trypan blue) and proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] tests. Intergroup comparisons were performed using two-way analysis of variance and the Tukey post hoc test (software GraphPad Prism 7.0).

Results: In the trypan blue test, the total number of cells was significantly different between the irradiated groups and the CG at all times studied. The total number of cells increased in laser group (LG)1 (0.84 J) and LG2 (1.40 J) and decreased in LG4 (6.72 J). The mitochondrial activity increased significantly in LG1 and LG2 at 48 and 72 h and decreased in LG3 (5.88 J) and LG4 (6.72 J) compared with CG.

Conclusions: The results indicate that the lower doses (0.45 and 0.75 J/cm2 ) of PBM induce the highest mitochondrial activity and cellular viability. Keywords: dose/response curve, photobiomodulation, red laser, fibroblasts, in vitro study


ATTENUATION AND PENETRATION OF VISIBLE 632.8nm AND INVISIBLE INFRA-RED 904nm LIGHT IN SOFT TISSUES

Chukuka S. Enwemeka, Ph.D., FACSM Department of Physical Therapy & Rehabilitation Sciences, University of Kansas Medical Center, Kansas City, KS, and Department of Veterans Affairs Medical Center, Kansas City, MO, U.S.A.

We studied the depth of penetration and the magnitude of attenuation of 632.8nm and 904nm light in skin, muscle, tendon, and cartilagenous tissues of live anaesthetized rabbits. Tissue specimens were dissected, prepared, and their thicknesses measured. Then, each wavelength of light was applied. Simultaneously, a power meter was used to detect and measure the amount of light transmitted through each tissue. All measurements were made in the dark to minimize interference from extraneous light sources. To determine the influence of pulse rate on beam attenuation, the 632.8nm light was used at two predetermined settings of the machine; continuous mode and 100 pulses per second (pps), at an on:off ratio of 1:1. Similarly, the 904nm infra-red light was applied using two predetermined machine settings: 292 pps and 2,336 pps. Multiple regression analysis of the data obtained showed significant positive correlations between tissue thickness and light attenuation (p < .001). Student's t-tests revealed that beam attenuation was significantly affected by wavelength. Collectively, our findings warrant the conclusions that (1) The calf muscles of the New Zealand white rabbit attenuates light in direct proportion to its thickness. In this tissue, light attenuation is not significantly affected by the overlying skin, a finding which may be applicable to other muscles. (2) The depth of penetration of a 632.8nm and 904nm light is not related to the average power of the light source. The depth of penetration is the same notwithstanding the average power of the light source. (3) Compared to the 904nm wavelength, 632.8nm light is attenuated more by muscle tissue, suggesting that is is absorbed more readily than the 904nm wavelength or conversely that the 904nm wavelength penetrates more. Thus, wavelength plays a critical role in the depth of penetration of light.

key words: Laser Therapy, Light Attenuation, Light Asorption.


Photomed Laser Surg. 2012 Dec;30(12):688-94. doi: 10.1089/pho.2012.3306. Epub 2012 Oct 1.


Skin penetration time-profiles for continuous 810�nm and Superpulsed 904 nm lasers in a rat model.

Joensen JOvsthus KReed RKHummelsund SIversen VVLopes-Martins R�Bjordal JM.

Abstract

Objectives: The purpose of this study was to investigate the rat skin penetration abilities of two commercially available low-level laser therapy (LLLT) devices during 150 sec of irradiation.

Background Data: Effective LLLT irradiation typically lasts from 20â€�sec up to a few minutes, but the LLLT time-profiles for skin penetration of light energy have not yet been investigated.

Methods: Sixty-two skin flaps overlaying rat's gastrocnemius muscles were harvested and immediately irradiated with LLLT devices. Irradiation was performed either with a 810 nm, 200 mW continuous wave laser, or with a 904â€�nm, 60 mW superpulsed laser, and the amount of penetrating light energy was measured by an optical power meter and registered at seven time points (range, 1-150 sec).

Results: With the continuous wave 810â€�nm laser probe in skin contact, the amount of penetrating light energy was stable at â�¼20% (SEM±0.6) of the initial optical output during 150â€�sec irradiation. However, irradiation with the superpulsed 904â€�nm, 60â€�mW laser showed a linear increase in penetrating energy from 38% (SEM±1.4) to 58% (SEM±3.5) during 150â€�sec of exposure. The skin penetration abilities were significantly different (p<0.01) between the two lasers at all measured time points.

Conclusions: LLLT irradiation through rat skin leaves sufficient subdermal light energy to influence pathological processes and tissue repair. The finding that superpulsed 904 nm LLLT light energy penetrates 2-3 easier through the rat skin barrier than 810â€�nm continuous wave LLLT, corresponds well with results of LLLT dose analyses in systematic reviews of LLLT in musculoskeletal disorders. This may explain why the differentiation between these laser types has been needed in the clinical dosage recommendations of World Association for Laser Therapy.


Photomedicine and Laser Surgery Volume 31, Number 4, 2013

Penetration of Laser Light at 808 and 980nm in Bovine Tissue Samples

Donald E. Hudson, BSEE, Doreen O. Hudson, BS, CET, James M. Wininger, BSEE, and Brian D. Richardson, BA, JD


Abstract

Objective: The purpose of this study was to compare the penetration of 808 and 980nm laser light through bovine tissue samples 18â€�95mm thick.

Background Data: Low-level laser therapy (LLLT) is frequently used to treat musculoskeletal pathologies. Some of the therapeutic targets are several centimeters deep.

Methods: Laser light at 808 and 980nm (1 W/cm2) was projected through bovine tissue samples ranging in thickness from 18 to 95 mm. Power density measurements were taken for each wavelength at the various depths.

Results: For 808 nm, 1 mW/cm2 was achieved at 3.4 cm, but for 980 nm, 1 mW/cm2 was achieved at only 2.2 cm depth of tissue.

Conclusions: It was determined that 808nm of light penetrates as much as 54% deeper than 980nm light in bovine tissue.


Skin Penetration Time-Profiles for Continuous 810nm and Superpulsed 904nm Lasers in a Rat Model

Jon Joensen, P.T., M.Sc.,1,2 Knut �vsthus, MIng, Ph.D.,3 Rolf K. Reed, M.D., Ph.D.,4, Steinar Hummelsund, P.T., M.Sc.,1 Vegard V. Iversen, Phys., Ph.D.,5, Rodrigo A´ lvaro Branda�o Lopes-Martins, Ph.D.,6 and Jan Magnus Bjordal, P.T., Ph.D.1,2

Objective: The purpose of this study was to investigate the rat skin penetration abilities of two commercially available low-level laser therapy (LLLT) devices during 150 sec of irradiation.

Background Data: Effective LLLT irradiation typically lasts from 20 sec up to a few minutes, but the LLLT time-profiles for skin penetration of light energy have not yet been investigated.

Materials and Methods: Sixty-two skin flaps overlaying ratâ€�s gastrocnemius muscles were harvested and immediately irradiated with LLLT devices. Irradiation was performed either with a 810 nm, 200mW continuous wave laser, or with a 904 nm, 60mW superpulsed laser, and the amount of penetrating light energy was measured by an optical power meter and registered at seven time points (range, 1â€�150 sec).

Results: With the continuous wave 810nm laser probe in skin contact, the amount of penetrating light energy was stable at *20% (SEM â€� 0.6) of the initial optical output during 150 sec irradiation. However, irradiation with the superpulsed 904 nm, 60mW laser showed a linear increase in penetrating energy from 38% (SEM â€� 1.4) to 58% (SEM â€� 3.5) during 150 sec of exposure. The skin penetration abilities were significantly different ( p < 0.01) between the two lasers at all measured time points.

Conclusions: LLLT irradiation through rat skin leaves sufficient subdermal light energy to influence pathological processes and tissue repair. The finding that superpulsed 904nm LLLT light energy penetrates 2â€�3 easier through the rat skin barrier than 810nm continuous wave LLLT, corresponds well with results of LLLT dose analyses in systematic reviews of LLLT in musculoskeletal disorders. This may explain why the differentiation between these laser types has been needed in the clinical dosage recommendations of World Association for Laser Therapy.


The recommended dosage (WALT) for anti inflammatory effect

Laser classes 3 or 3 B, 780 -860nm GaAlAs Lasers. Continuous or pulse output less than 0.5 Watt Energy dose delivered to the skin over the target tendon or synovia

Tendinopathies Points/cm2 Joules Notes
Carpal-tunnel 2-3 12 Minimum 6 Joules per point
Lateral epicondylitis 1-2 4 Maximum 100mW/cm2
Biceps humeri c.l. 1-2 8  
Supraspinatus 2-3 10 Minimum 5 Joules per point
Infraspinatus 2-3 10 Minimum 5 Joules per point
Trochanter major 2-4 10  
Patellartendon 2-3 6  
Tract. Iliotibialis 2-3 3 Maximum 100mW/cm2
Achilles tendon 2-3 8 Maximum 100mW/cm2
Plantar fasciitis 2-3 12 Minimum 6 Joules per point

Arthritis Points/cm2 Joules Notes
Finger PIP or MCP 1-2 6  
Wrist 2-4 10  
Humeroradial joint 1-2 4  
Elbow 2-4 10  
Glenohumeral joint 2-4 15 Minimum 6 Joules per point
Acromioclavicular 1-2 4  
Temporomandibular 1-2 6  
Cervical spine 2-4 15 Minimum 6 Joules per point
Lumbar spine 2-4 40 Minimum 8 Joules per point
Hip 2-4 40 Minimum 8 Joules per point
Knee medial 3-6 20 Minimum 5 Joules per point
Ankle 2-4 15  

Laser classes 3 or 3B, 904 nm GaAs Lasers (Peak pulse output more than 1 Watt) Energy dose delivered to the skin over the target tendon or synovia

Tendinopathies Points/cm2 Joules Notes
Carpal-tunnel 2-3 4 Minimum 2 Joules per point
Lateral epicondylitis 1-2 1 Maximum 100mW/cm2
Biceps humeri c.l. 1-2 2  
Supraspinatus 2-3 3 Minimum 2 Joules per point
Infraspinatus 2-3 3 Minimum 2 Joules per point
Trochanter major 2-3 2  
Patellartendon 2-3 2  
Tract. Iliotibialis 2-3 2 Maximum 100mW/cm2
Achilles tendon 2-3 2 Maximum 100mW/cm2
Plantar fasciitis 2-3 3 Minimum 2 Joules per point

Arthritis Points/cm2 Joules Notes
Finger PIP or MCP 1-2 2  
Wrist 2-3 3  
Humeroradial joint 1-2 2  
Elbow 2-3 3  
Glenohumeral joint 2-3 6 Minimum 2 Joules per point
Acromioclavicular 1-2 2  
Temporomandibular 1-2 2  
Cervical spine 2-3 6 Minimum 2 Joules per point
Lumbar spine 2-3 10 Minimum 4 Joules per point
Hip 2-3 10 Minimum 4 Joules per point
Knee anteromedial 2-4 6 Minimum 2 Joules per point
Ankle 2-4 6  

Daily treatment for 2 weeks or treatment every other day for 3-4 weeks is recommended Irradiation should cover most of the pathological tissue in the tendon/synovia.

Tendons

Start with energy dose in table, then reduce by 30% when inflammation is under control (Does not apply for carpal tunnel tendo synovitis)

Therapeutic windows range from typically +/-50% of given values Recommended doses are based on ultrasonographic measurements of depths from skin surface and typical volume of pathological tissue and estimated optical penetration for the different laser types in caucasians.

Disclaimer: The list may be subject to change at any time when more research trials are being published. World Association of Laser Therapy is not responsible for the application of laser therapy in patients, which should be performed at the therapist/doctor`s discretion and responsibility

Revised August 2005


 BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY


Ying-Ying Huang  Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Department of Dermatology, Harvard Medical School, Boston, MA; Aesthetic and Plastic Center of Guangxi Medical University, Nanning, P.R. China
Aaron C.-H. Chen  Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Boston University School of Medicine, Graduate Medical
Sciences, Boston, MA
James D. Carroll  THOR Photomedicine Ltd, 18A East Street, Chesham, HP5 1HQ, UK
Michael R. Hamblin  Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Department of Dermatology, Harvard Medical
School, Boston, MA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA


The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many
positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.



1. INTRODUCTION
1.1. Brief history
Low level laser therapy (LLLT) is the application of light (usually a low power laser or LED in the range of 1mW – 500mW) to a pathology to promote tissue regeneration, reduce inflammation and relieve pain. The light is typically of narrow spectral width in the red or near infrared Dose-Response (Prepress)
Formerly Nonlinearity in Biology, Toxicology, and Medicine Copyright © 2009 University of Massachusetts
ISSN: 1559-3258
DOI: 10.2203/dose-response.09-027.Hamblin
Address correspondence to Professor Michael R. Hamblin, BAR 414, Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114; Phone: 617-726-6182, Fax: 617-726-8566, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. 

(NIR) spectrum (600nm – 1000nm), with a power density (irradiance) between 1mw-5W/cm2. It is typically applied to the injury for a minute or
so, a few times a week for several weeks. Unlike other medical laser procedures, LLLT is not an ablative or thermal mechanism, but rather a photochemical.