Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term “low level laser therapy” or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy.

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The Nuts and Bolts of Low-level Laser (Light) Therapy

Understanding wound healing today involves much more than simply stating that there are three phases: inflammation, proliferation, and maturation. Wound healing is a complex series of reactions and interactions among cells and "mediators." Each year, new mediators are discovered and our understanding of inflammatory mediators and cellular interactions grows. This article will attempt to provide a concise overview on wound healing and wound management.

Wound healing: an overview.

Background Given the recent interest in light-emitting diode (LED) photomodulation and minimally invasive nonablative laser therapies, it is timely to investigate reports that low-level laser therapy (LLLT) may have utility in wound healing.

Objectives To critically evaluate reported in vitro models and in vivo animal and human studies and to assess the qualitative and quantitative sufficiency of evidence for the efficacy of LLLT in promoting wound healing.

Method Literature review, 1965 to 2003.

Results In examining the effects of LLLT on cell cultures in vitro, some articles report an increase in cell proliferation and collagen production using specific and somewhat arbitrary laser settings with the helium neon (HeNe) and gallium arsenide lasers, but none of the available studies address the mechanism, whether photothermal, photochemical, or photomechanical, whereby LLLT may be exerting its effect. Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound healing found in small case series have not been replicated in larger studies.

Conclusion To better understand the utility of LLLT in cutaneous wound healing, good clinical studies that correlate cellular effects and biologic processes are needed. Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time. Although applications of high-energy (10–100 W) lasers are well established with significant supportive literature and widespread use, conflicting studies in the literature have limited low-level laser therapy (LLLT) use in the United States to investigational use only. Yet LLLT is used clinically in many other areas, including Canada, Europe, and Asia, for the treatment of various neurologic, chiropractic, dental, and dermatologic disorders. To understand this discrepancy, it is useful to review the studies on LLLT that have, to date, precluded Food and Drug Administration approval of many such technologies in the United States. The fundamental question is whether there is sufficient evidence to support the use of LLLT.

WILLIAM POSTEN, MD, DAVID A. WRONE, MD, JEFFREY S. DOVER, MD, FRCPC, KENNETH A. ARNDT, MD, SIRUNYA SILAPUNT, MD, AND MURAD ALAM, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

Low-Level Laser Therapy for Wound Healing: Mechanism and Efficacy

The aim of this work is to review the available literature on the details of low-level laser therapy (LLLT) use for the enhancement of the proliferation of various cultured cell lines including stem cells. A cell culture is one of the most useful techniques in science, particularly in the production of viral vaccines and hybrid cell lines. However, the growth rate of some of the much-needed mammalian cells is slow. LLLT can enhance the proliferation rate of various cell lines. Literature review from 1923 to 2010. By investigating the outcome of LLLT on cell cultures, many articles report that it produces higher rates of ATP, RNA, and DNA synthesis in stem cells and other cell lines. Thus, LLLT improves the proliferation of the cells without causing any cytotoxic effects. Mainly, helium neon and gallium-aluminum-arsenide (Ga-Al-As) lasers are used for LLLT on cultured cells. The results of LLLT also vary according to the applied energy density and wavelengths to which the target cells are subjected. This review suggests that an energy density value of 0.5 to 4.0 J/cm2 and a visible spectrum ranging from 600 to 700 nm of LLLT are very helpful in enhancing the proliferation rate of various cell lines. With the appropriate use of LLLT, the proliferation rate of cultured cells, including stem cells, can be increased, which would be very useful in tissue engineering and regenerative medicine.

Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells

In this study we have evaluated the use of blue light (peak at 415 nm) and a mixed blue and red light (peaks at 415 and 660 nm) in the treatment of acne vulgaris. One hundred and seven patients with mild to moderate acne vulgaris were randomized into four treatment groups: blue light, mixed blue and red light, cool white light and 5% benzoyl peroxide cream. Subjects in the phototherapy groups used portable light sources and irradiation was carried out daily for 15 min. Comparative assessment between the three light sources was made in an observer-blinded fashion, but this could not be achieved for the use of benzoyl peroxide. Assessments were performed every 4 weeks. After 12 weeks of active treatment a mean improvement of 76% (95% confidence interval 66-87) in inflammatory lesions was achieved by the combined blue-red light phototherapy: this was significantly superior to that achieved by blue light (at weeks 4 and 8 but not week 12), benzoyl peroxide (at weeks 8 and 12) or white light (at each assessment). The final mean improvement in comedones by using blue-red light was 58% (95% confidence interval 45-71), again better than that achieved by the other active treatments used, although the differences did not reach significant levels. We have found that phototherapy with mixed blue-red light, probably by combining antibacterial and anti-inflammatory action, is an effective means of treating acne vulgaris of mild to moderate severity, with no significant short-term adverse effects.

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Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris.

This paper briefly reviews the authors' experimental and clinical use of lasers over a 20-year period, during which laser effects on 15 biological systems were studied. Low-energy laser radiation was found to have a stimulating effect on cells, and high-energy radiation had an inhibiting effect. The application of lasers to stimulate wound healing in cases of nonhealing ulcers is recommended.

The biomedical effects of laser application.

The History of Photobiomodulation: Endre Mester (1903-1984).

One of the most significant discoveries of present medical engineering is that of the laser. It involves new, almost inconcievable perspectives in the fields of biological research and applications in the medical practice. In the very early time of the laser, there was a great expectation in connection with it’s special burning, vaporizing and coagulating effect. This idea proved to be true in the medical practice many times.

Mester’s Method of Laser Biostimulation

Since the first ruby laser was made in 1960, multiple applications of lasers have been identified. The special burning, coagulating, and vaporizing effects of high output lasers, together with their easy manipulation using optical systems, have resulted in extensive medical use. Additionally, there is much interest in the nonthermic effects of lasers in photodynamic tumor therapy and in biostimulation.

Data for Laser Biostimulation in Wound-Healing

The following biological systems and physiologic processes were influenced by a variety of low-output lasers: 1) Repeated laser irradiation of the skin 2) Hair growth in depilated mice 3) Phagocytosis of bacteria by human and rat leukocytes 4) Spontaneous activity of jejunal villi in dogs 5) Neurotransmitter release following ruby laser exposure in guinea-pig ileum 6) DNA and RNA content in ruby laser irradiated Escherichia coli cultures 7) Laser irradiation on Ehrlich’s ascites tumor cells 8) Remote effect of laser irradiation on vessel formation in rabbit cornea 9) Low-output laser irradiation and wound healing: A) electronmicroscopy of granulation tissue: collagen production in fibroblasts B) enzymatic events in the early stages of wound healing C) regeneration of microcirculation in rabbit ear D) regeneration of muscle fiber E) tensile strength of He-Ne laser-irradiated wounds in rat’s skin F) immunosuppressive effect of laser-irradiation: – skin allotransplant survival time in rat – blast formation of phytohemagglutine stimulated lumphocytes – effect of noncoherent light sources on T and B lymphocytes G) prostaglandin content in wounded dorsal skin of the rat Biostimulatory effects of low-output laser irradiation have been demonstrated at a variety of molecular and cellular levels, as well as at whole organ and tissue levels. Under certain circumstances, syner-gistic effects with laser irradiation have been demonstrated; e.g. an effect on the immune system. Evidence exists which indicate that effects remote to the irradiated site occur, suggesting the presence of a circulatory active substance. Furthermore, the biostimulatory effects of low-output laser irradiation are dose dependent and, with sufficient intensity, the stimulatory effect disappears and inhibition occurs.The following biological systems and physiologic processes were influenced by a variety of low-output lasers: 1) Repeated laser irradiation of the skin 2) Hair growth in depilated mice 3) Phagocytosis of bacteria by human and rat leukocytes 4) Spontaneous activity of jejunal villi in dogs 5) Neurotransmitter release following ruby laser exposure in guinea-pig ileum 6) DNA and RNA content in ruby laser irradiated Escherichia coli cultures 7) Laser irradiation on Ehrlich’s ascites tumor cells 8) Remote effect of laser irradiation on vessel formation in rabbit cornea 9) Low-output laser irradiation and wound healing: A) electronmicroscopy of granulation tissue: collagen production in fibroblasts B) enzymatic events in the early stages of wound healing C) regeneration of microcirculation in rabbit ear D) regeneration of muscle fiber E) tensile strength of He-Ne laser-irradiated wounds in rat’s skin F) immunosuppressive effect of laser-irradiation: – skin allotransplant survival time in rat – blast formatio...

Adam Mester

Papers

The biomedical effects of laser application.

The History of Photobiomodulation: Endre Mester (1903-1984).

Mester’s Method of Laser Biostimulation

Data for Laser Biostimulation in Wound-Healing

Basic research in biostimulation