Low Level Laser Therapy Mechanisms and Applications

Review Article

Low Level Laser Therapy Mechanisms and Applications

Corresponding authorDr. Hady Atef, Lecturer assistant at department of physical therapy for cardiovascular/respiratory disorders and geriatrics, Faculty of physical therapy, Cairo University, Egypt ,
Tel: +21119699110 ; Email: Hady612@hotmail.com


Definition of LASER

A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The term “laser” originated as an acronym for “light amplification by stimulated emission of radiation”. A laser differs from ot her sources of light in that it emits light coherently. Spatial coherence allows a laser to be focused to a tight spot, enabling applications such as laser cutting and lithography. Spatial coherence also allows a laser beam to stay narrow over great distances (collimation), enabling applications such as laser pointers. Lasers c a n also have high temporal coherence, which allows them to emit light with a very narrow spectrum, i.e., they can emit a single color of light. Temporal coherence can be used to produce pulses of light as short as a femtosecond [1].

Classification of LASER

The classification system as specified by the International electrochemical commission (IEC) 60825-1 standard (IEC, 2007). Classes 1,1M,2,2M,3R are considered as low level laser, while classes 3B, and 4 can be considered as high level laser [2].

Low level laser therapy( LLLT)

Low-level laser therapy (LLLT) is a form of laser medicine used in physical t h e r a p y and veterinary treatment that uses low-level (low- power) lasers or light-emitting diodes to alter cellular function. Other names for the therapy include low-power laser, soft laser, cold laser, biostimulation laser, therapeutic laser, and laser acupuncture. Whereas high-power lasers ablate tissue, low-power lasers are claimed to stimulate it and to encourage the cells to function [3].

LLLT is integrated with mainstream medicine with ongoing research to determine where there is a demonstrable effect. Areas of dispute include the ideal location of treatment (specifically whether LLLT is more appropriately used over nerves versus joints), dose, wavelength, timing, pulsing and duration. The effects of LLLT appear to be limited to a specified set of wavelengths of laser, and administering LLLT below the dose range does not appear to be effective [4].

Low level laser classification:

There are three diode types. The first is an Indium, Gallium-Aluminum-Phosphide (InGaAlP) laser. This is a visible redlight laser diode that operates in the 630-700 nm range. These lasers output light continuously. These lasers also might be pulsed by an electro-mechanical method (duty cycle). A duty cycle output means the power is switched off for part of a second and then switched back on. If it was off for a ½ second and on for a ½ second, that would be referred to as a 50 percent duty cycle. This reduces the average power output by 50 percent. Red-light lasers have the least amount of penetration of the three lasers with a range of 6-10 mm. They affect the skin and superficial tissue [5].

The second semiconductor laser is a Gallium-Aluminum Arsenide (GaAlAs) laser. This is a near-infrared laser, which means that the light emission is invisible to the naked eye. This laser operates in the 780-890 nm range. This type of laser also has a continuous output of power and is often pulsed on a duty cycle as described above. This laser penetrates 2-3 cm in depth. These lasers often are utilized for medium to deep tissue structures such as muscles, tendons and joints [5].

The third semiconductor laser is a Gallium-Arsenide (GaAs) laser. This laser is unique in that it always is operated in superpulsed mode. Superpulsing means the laser produces very short pulses of high peak power. These peak power spikes usually are in the 10-100 watt range, but last for only 100-200 nanoseconds while maintaining a mean power output that is relatively low. This phenomenon is similar to what happens in a camera flash. Superpulsing allows for deep penetration into body tissues without causing the unwelcome tissue effects of continuous high-power output, such as heat production. Superpulsing allows for deeper penetration than a laser of the same wavelength that is not superpulsed, but has the same average output power. Penetration is 3-5 cm or more. Superpulsing also allows for treatment times to be the shortest possible. These lasers are extremely well-suited for medium and deep tissues, such as tendons, ligaments and joints [5].

Evidence for effectiveness of LLLT

Since 1967 over 100 phase III, randomized, double-blind, placebocontrolled, clinical trials (RCTs) have been published and supported by over 1,000 laboratory studies investigating the primary mechanisms and the cascade of secondary effects that contribute to a range of local tissue and systemic effects [6].

RCTs with positive outcomes have been published on pathologies as diverse as osteoarthritis ,tendonopathies ,wounds, back pain ,neck pain,muscle fatigue, peripheral nerve injuries and; nevertheless results have not always been positive. This failure in certain circumstances can be attributed to several factors including dosimetry (inadequate or too much energy delivered, inadequate or too much irradiance, inappropriate pulse structure, irradiation of insufficient area of the pathology), inappropriate anatomical treatment location and concurrent patient medication (such as steroidal and non-steroidal anti-inflammatories which can inhibit healing) [7].

Technique of application

There are two major types of lasers, contact and noncontact, used in medicine. Contact lasers work by sending a light through a fiber or sapphire tip. The tip absorbs energy and becomes hot. When the hot tip touches any live tissue in the body, the target cells are vaporized, which is the removal of tissue through the conversion of a solid to a gas. Noncontact lasers do not touch the tissue. They operate by transferring laser light as radiant energy in a single beam to the tissue. Heat results when the cell absorbs this energy. In both cases, the laser light is not hot. Heat is only created after the laser’s radiant energy is absorbed by the targeted tissue [8].

Contact lasers can be used for cutting through bone as well as pulverizing kidney stones. A common contact laser is called the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. This laser can go deep into the tissue and even cause blood to clot. It is often used in cancer patients [9].

Some noncontact lasers are used with laser light-sensitive drugs. Such a drug is administered to a patient, and over time, the drug is absorbed into tumor cells only. By exposing the drug in the cancer cells to the laser, a chemical reaction occurs. This kills the cancer, but most healthy cells are not affected. This is called photodynamic therapy [10].

Mechanisms of action of low level light therapy

1. Cellular Chromophores and First Law of Photobiology

The first law of photobiology states that for low power visible light to have any effect on a living biological system, the photons
must be absorbed by electronic absorption bands belonging to some molecular photoacceptors, or chromophores [11]. A chromophore is a molecule (or part of a molecule) which imparts some decided color to the compound of which it is an ingredient. Chromophores almost always occur in one of two forms: conjugated pi electron systems and metal complexes [12].

Examples of such chromophores can be seen in chlorophyll (used by plants for photosynthesis), hemoglobin, cytochrome  c oxidase (Cox), myoglobin, flavins, flavoproteins and porphyrins [13].

2. Action Spectrum and Tissue Optics

Irradiation Time Or Energy Delivered (The Dose)
Irradiation Unit of Parameter measurement Energy (Joules) J Calculated as: Energy (J) = Power (W) x time (s)

This mixes medicine and dose into a single expression and ignores Irradiance. Using Joules as an expression of dose is potentially unreliable as it assumes reciprocity (the inverse relationship between power and time) [14].

Energy Density J/cm2 Common expression of LLLT ―dose is Energy Density(14).

This optical window runs approximately from 650 nm to 1200 nm. The absorption and scattering of light in tissue are both much higher in the blue region of the spectrum than the red, because the principle tissue chromophores (hemoglobin and melanin) have high absorption bands at shorter wavelengths,- tissue scattering of light is higher at shorter wavelengths, and furthermore water strongly absorbs infrared light at wavelengths greater than 1100-nm. Therefore the use of LLLT in animals and patients almost exclusively involves red and near-infrared light (600-1100-nm) [15].

Phototherapy is characterized by its ability to induce photobiological processes in cells. Exact action spectra are needed for determination of photoacceptors as well as for further investigations into cellular mechanisms of phototherapy. The action spectrum shows which specific wavelength of light is most effectively used in a specific chemical reaction [16].

3. Mitochondrial Respiration and ATP

Current research about the mechanism of LLLT effects inevitably involves mitochondria. Mitochondria play an important role in energy generation and metabolism. Mitochondria are sometimes described as―cellular power plants, because they convert food molecules into energy in the form of ATP via the process of oxidative phosphorylation. Several pieces of evidence suggest that mitochondria are responsible for the cellular response to red visible and near infrared (NIR) light. The effects of HeNe laser and other illumination on mitochondria isolated from rat liver, have included increased proton electrochemical potential, more ATP synthesis, increased RNA and protein synthesis and increases in oxygen consumption, membrane potential, and enhanced synthesis of NADH and ATP [17].

4. Cytochrome c oxidase and nitric oxide release

Absorption spectra obtained for cytochrome c oxidase (Cox) in different oxidation states were recorded and found to be very similar to the action spectra for biological responses to light .Therefore it was proposed that Cox is the primary photoacceptor for the red-NIR range in mammalian cells [18].

5. Nitric oxide signaling

In addition to NO being photodissociated from Cox as described, it may also be photo-released from other intracellular stores such as nitrosylated hemoglobin and nitrosylated myoglobin [19].Light mediated vasodilation was first described in 1968 by Furchgott, in his nitric oxide research that lead to  his receipt of a Nobel Prize thirty years later in 1998.Later studies conducted by other researchers confirmed and extended Furchgott’s early work and demonstrated the ability of light influence the localized production or release of NO and stimulate vasodilation through the effect NO on cyclic guanine [20].6. Reactive oxygen species and gene transcriptionReactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the signaling pathways from mitochondria to nuclei.Reactive oxygen species (ROS) are very small molecules that include oxygen ions such as superoxide, free radicals such as hydroxyl radical, and hydrogen peroxide, and organic peroxides. They are highly with biological molecules such as proteins, nucleic acids and unsaturated lipids. ROS form as a natural by-product of the normal metabolism of oxygen and have important roles in cell signaling [20],regulating nucleic acid synthesis, protein synthesis, enzyme activation and cell cycle progression [21].

LLLT was reported to produce a shift in overall cell redox potential in the direction of greater oxidation and increased ROS generation and cell redox activity have been demonstrated these cytosolic responses may in turn induce transcriptional changes. Several transcription factors are regulated by changes in cellular redox state. But the most important one is nuclear factor B (NF-B) [22-27].

7. Downstream cellular response

Although the underlying mechanism of LLLT are still not completely  understood, in vitro studies, animal experiments and clinical studies have all tended to indicate that LLLT delivered at low doses may produce a better result when compared to the same light delivered at high doses. LLLT can prevent cell apoptosis and improve cell proliferation, migration and adhesion at low levels of red/NIR light illumination. LLLT at low doses has been shown to enhance cell proliferation in vitro in several types of cells: fibroblasts ,keratinocytes, endothelial cells and lymphocytes [28].

The mechanism of proliferation was proposed to involve photostimulatory effects in mitochondria processes, which enhanced growth factor release,and ultimately led to cell proliferation [29].

8. Downstream tissue response

There have been a large number of both animal model and clinical studies that demonstrated highly beneficial LLLT effects on a variety of diseases, injuries, and has been widely used in both chronic and acute conditions .It may enhance neovascularisation, promote angiogenesis and increase collagen synthesis to promote healing of acute and chronic wounds [30]. It provided acceleration of cutaneous wound healing in rats with a biphasic dose response favoring lower doses [31].

It can also stimulate healing of deeper structures such as nerves [32],tendons [33], cartilage[34], bones[35] and even  internal organs [36]. LLLT can reduce pain [36], inflammation [36] and swelling [37] caused by injuries, degenerative diseases or autoimmune diseases. Oron reported beneficial effect of LLLT on repair processes after injury or ischemia in skeletal and heart muscles in multiple animal models in vivo [38-41]. LLLT has been used to mitigate damage after strokes (in both animals [42] and humans) [43], after traumatic brain injury [44] and after spinal cord injury [45].


The North American Association for Laser Therapy ( NAALT) has compiled the following list of contraindications: pregnancy (over the pregnant uterus), cancers (over the tumor site), where treatment would be over the thyroid gland, where treatment would be over pediatric joint epiphysis, transplant patients, or other immuno-suppressed patients, and photosensitive patients [46].

Caution should be used when considering the use of laser phototherapy on patients that have recently under gone steroid or Botox treatment [47].


1.Ad N,Oron U. Impact of low level laser irradiation on infarct size in the rat following myocardial infarction. Int J Cardiol. 2001, (80):109-116.

2.International electrochemical association (IEC), 2007.

3.Joensen J, Ovsthus K, Reed R K, Hummelsund S, Iversen V V et al. Skin Penetration Time-Profiles for Continuous 810 nm and Superpulsed 904 nm Lasers in a Rat Model. Photomed Laser Surg. 2012, 30 (12):688-694.

4.Karu TI, Afanas’eva NI. Cytochrome c oxidase as the primary photoacceptor upon laser exposure of cultured cells to visible and near IR-range light. Dokl Akad Nauk; 1999, 342(5): 693-695.

5.Lampl Y, Zivin JA, Fisher M, Lew R, Welin L et al. Infrared Laser Therapy for Ischemic Stroke: A New Treatment Strategy. Results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1); Stroke. 2006, 38(6): 1843-1849.

6.Lapchak PA, Han MK, Salgado KF, Streeter J, and Zivin JA. Safety profile of transcranial near-infrared laser therapy administered in combination with thrombolytic therapy to embolized rabbits.Stroke. 2008, 39(11):3073-3078.

7.Lubart R, Eichler M, Lavi R, Friedman H, and Shainberg A. (2005): Low-energy laser irradiation promotes cellular redox activity. British Journal of Anaesthesia ;( 94):123-126.

8.Mitchell UH, Mack GL. Low-level laser treatment with near- infrared light increases venous nitric oxide levels acutely: a single-blind, randomized clinical trial of efficacy, Am J Phys Med Rehabil, 2013, 92(2):151-156.

9.Morrone G, Guzzardella GA, Torricelli P, Rocca M et al. Osteochondral lesion repair of the knee in the rabbit after low-power diode Ga-Al-As laser biostimulation: an experimental study Artif Cells Blood Substit Immobil Biotechnol. 2000, 28(4): 321-336.

10.Mueller X, Tinguely F, Tevaearai H. Pain location, distribution, and intensity after cardiac surgery. Chest. 2000, 118(2):391–396.

11.Oron U, Yaakobi T, Oron A, Hayam G, Gepstein L et al. Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Lasers Surg Med. 2001, 28(3):204-211.

12.Oron U, Yaakobi T, Oron A, Mordechovitz D, Shofti R et al. Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs. Circulation. 2001, 103(2):296-301.

13.Pal G, Dutta A, Mitra K, Grace MS, Romanczyk TB et al. Effect of low intensity laser interaction with human skin. J Photochem Photobiol B. 2007, 86(3):252-261.

14.Paul .Myeloid dendritic cells isolated from tissues of SIV-infected Rhesus macaques promote the induction of regulatory T cells” ,AIDS, 2012, 28,26 (3):262-273.

15.Shiva S and Gladwin MTShining a light on tissue NO stores: near infrared release of NO from nitrite and nitrosylated hemes. J Mol Cell Cardiol . 2009, (46):1-3.

16.Sommer AP, Pinheiro AL, Mester AR, Franke RP, Whelan HT. Biostimulatory windows in low-intensity laser activation: lasers, scanners, and NASA’s light-emitting diode array system. J Clin Laser Med Surg. 2001, 19(1):29-33.

17.Stadler I, Evans R, Kolb B, Naim JO, Narayan V, Buehner N,metalloand Lanzafame RJ. In vitro effects of low-level laser irradiation at 660 nm on peripheral blood lymphocytes, Lasers Surg Med. 2000, 27(3):255-261.

18.Storz P,Mitochondrial ROS–radical detoxification, mediated by protein kinase D. Trends Cell Biol .2007, (17):13-18.

19.Sutherland JC. Biological effects of polychromatic light. Photochem Photobiol . 2002, 76(2): 164-170.

20.Tafur J, Mills PJ. Low-intensity light therapy: exploring the role of redox mechanisms.Photomed Laser Surg. 2008, 26(4):323-328.

21.Tuner J, Hode L. The Laser Therapy Handbook . Prima Books, 2004. Sweden. pg 24.

22.Verma S, Fedak PWMS, Weisel RD, Butany J, Rao V et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation .2002, 105(20):2332–2345.

23.Weber JB, Pinheiro AL, de Oliveira MG, Oliveira FA, and Ramalho LM. Laser therapy improves healing of bone defects submitted to autologous bone graft. Photomed Laser Surg.2006, 24(1):38-44.

24.William J. Journal of pain management. 2006, December issue.;1-4.

25.Wu S, Xing D, Gao X, Chen WR. High fluence low-power laser irradiation induces mitochondrial permeability transition mediated by reactive oxygen species. J Cell Physiol .2009, 218(3):603-611.

26.Yaakobi T, Shoshany Y, Levkovitz S, Rubin O, Ben Haim SA et al. Long-term effect of low energy laser irradiation on infarction and reperfusion injury in the rat heart. J Appl Physiol. 2001, 90(6):2411-2419.

27.Zhang J, Xing D, Gao X. Low-power laser irradiation activates Src tyrosine kinase through reactive oxygen species-mediated signaling pathway. J Cell Physiol. 2008, 217(2):518-528

28.Congenital Heart Defects

29.Zivin JA, Albers GW, Bornstein N, Chippendale T, Dahlof B et al. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke. 2009, 40(4):1359- 1364.

30.Aimbire F, Albertini R, Pacheco MT, Castro-Faria-Neto HC, Leonardo PS et al. Low-level laser therapy induces dosedependent reduction of TNFalpha levels in acute inflammation. Photomed Laser Surg.2006, 24(1):33-37.

31.Alexandratou E, Yova D, Handris P, Kletsas D, Loukas S.Human fibroblast alterations induced by low power laser ir radiation at the single cell level using confocal microscopy. Photochem Photobiol Sci.2002, (1):547-552.

32.Bjordal JM, Johnson MI, Lopes-Martins RA, Bogen B, Chow R et al. Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and metaanalysis of randomised placebo-controlled trials. BMC Musculoskelet Disord. 2007, 8:51.

33.WBjordal JM, Lopes-Martins RA, Iversen VV. A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. Br J Sports Med.2006, 40(1):76-80.

34.Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med .2003, 23, 349(17):1605–1613.

35.Brondon P, Stadler I, Lanzafame RJ.A study of the effects of phototherapy dose interval on photobiomodulation of cell cultures. Lasers Surg Med. 2005, 36(5):409-413.

36.Brown GC. Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta. 2001, 1504(1):46-57.

37.Carney DE, Lutz, CJ, Picone AL. Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass. Circulation .1999, 100(4):400-406.

38.Chen AC-H, Arany PR, Huang YY, Tomkinson EM, Saleem T et al. Low level laser therapy activates NF-κB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One. 2011. 2009, 6(7): e22453.

39.Coloumbo F, Bek EL, Yun KL, Kochamba GS et al. Essential Physical Medicine and Rehabilitation. Low level laser applications. 2013, (1): 22-24.

40.Corazza AV, Jorge J, Kurachi C, and Bagnato VS. Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources. Photomed Laser Surg. 2007, 25(2):102-106.

41.Debrouh Zion. Cell proliferation, reactive oxygen species. Dose response. 2006, 12:112-114.

42.Fillipin LI, Mauriz JL, Vedovelli K, Moreira AJ, Zettler CG, et al. Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon. Lasers Surg Med. 2005, 37(4):293-300.

43.Fonseca AS, Geller M, Bernardo Filho M, Valença SS, de Paoli F. Low-level infrared laser effect on plasmid DNA. Lasers Med Sci. 2012, 27(1):121-130. Gavish L, Perez L, Gertz SD. Low-level laser irradiation modulates matrix metalloand proteinase activity and gene expression in porcine aortic smooth muscle cells. Lasers Surg Med. 2006, (38):779- 786.

44.Gavish L, Perez L, and Gertz SD. Low-level laser irradiation modulates matrix metalloproteinase activity and gene expression in porcine aortic smooth muscle cells. Lasers Surg Med. 2006, 38(8):779-786.

45.Gigo-Benato D, Geuna S, de Castro Rodrigues A, Tos P, Fornaro M et al. Low-power laser biostimulation enhances nerve repair after end-to-side neurorrhaphy: a double-blind randomized study in the rat median nerve model. Lasers Med Sci. 2004, 19(1):57-65.

46.North American association of laser therapy (NAALT) standards, 2003.

47.North American association of laser therapy (NAALT) standards , Toronto conference, Canada, 2006.

Be the first to comment on "Low Level Laser Therapy Mechanisms and Applications"

Leave a comment

Your email address will not be published.