A renaissance in low-level laser (light) therapy – LLLT

This special issue on low-level laser (light) therapy (LLLT) has been assembled by soliciting individual contributions from a broad spectrum of specialists in the field throughout the world. LLLT also known as photobiomodulation, is the drug-free, non-invasive and safe (FDA approved) clinical application of light – usually produced by low to mid power lasers or light emitting diodes (LED) with a power output in the range of 1 – 500 mW – to a patient to promote tissue regeneration and healing, reduce inflammation and relieve pain. The light is typically of narrow spectral range (1 – 40 nm bandwidth), in the visible (red) or near infrared (NIR) spectrum (600 – 1000 nm), and achieves an average power density (irradiance) between 1 mW/cm 2 and 5 W/cm 2 [1] . The reason why the technique is termed “ lowlevel ” or “ cold laser ” therapy is that the optimum level of energy density (J/cm 2 ) delivered to the tissues is low when compared to other forms of laser therapy such as those used for ablation, cutting, and thermally coagulating tissue. In general, the power densities used for LLLT are lower than those needed to produce heating of tissue (i.e., < 100 mW/cm 2 , depending on wavelength and tissue type), and the total energy delivered to the treated area is usually below 10 J/cm 2 . A common reference is the “ Guidelines for Skin Exposure to Laser Light ” in the International Standards Manual (IEC-825) which considers an exposure below 200 mW/cm 2 as a safe exposure [2] . LLLT, i.e., the use of low levels of visible or NIR light for reduction of inflammation and pain [3] , healing of wounds, muscle and nerve injuries [4] , and prevention of tissue damage by reducing cellular apoptosis (for example, due to ischemia and reperfusion injury) [5] , has been known for almost 50 years since shortly after the invention of lasers in 1960 [6] . However, despite many reports of positive findings from experiments conducted in vitro , in animal models and in randomized controlled clinical trials, the mechanisms of LLLT in biological tissues remains not fully elucidated. It is likely this is due to two main reasons: firstly, the complexity in interpretation of scientific and clinical data generated in different labs and clinical settings, and secondly, inconsistency in the use of light sources (medical devices) and treatment protocols including, illumination parameters (such as wavelength, fluence, power density, pulse structure, etc.) and the treatment schedule. Unfortunately, these variations led to an increase in the number of negative studies and created some controversy despite the overwhelming number of positive clinical results [7] . It is noteworthy that many preclinical and clinical studies have been and still are conducted without proper scientific methodology. Therefore, it is critical that all the characteristics of the light emitted by lasers or LEDs must be specified if data are to be useful. A requirement for a good phototherapy study, using LLLT in the visible or NIR region, whether from a laser, an LED, or a filtered incandescent lamp is to specify everything about the light source, i.e., wavelength(s), total power, power density, total energy, fluence, coherence, pulse structure (both frequency and pulse duration), polarization, area of exposure, illumination time, and treatment repetition [8] . There are published experimental and clinical studies that were conducted with good scientific methodology, but they did not fully describe the light parameters, therefore these studies cannot be repeated or extended by another researcher. Such publications are useless. In recent years, major advances have been made in understanding the mechanisms that operate at the molecular, cellular and tissue levels during LLLT. Mitochondria are thought to be the main site for the initial effects of light. New discoveries in the last decade have significantly altered our view on mitochondria. They are no longer viewed as only energy-making cellular compartments but rather individual cells-within-the-cell that are involved in numerous signalling and second messenger pathways [9] . In particular, it has been suggested that many important cellular components such as specific enzymes and ion channels [for instance nitric oxide synthase (NOS), ATPdependent K + channels, and poly-(APD-ribose) polymerase, have a distinct, mitochondrial variant]. For example, the intriguing possibility that mitochondria are significant