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The use of low levels of visible or near infrared light (LLLT) for reducing pain, inflammation and edema, promoting
healing of wounds, deeper tissues and nerves, and preventing tissue damage by reducing cellular apoptosis has been
known for almost forty years since the invention of lasers. Originally thought to be a peculiar property of laser light
(soft or cold lasers), the subject has now broadened to include photobiomodulation and photobiostimulation using
non-coherent light. Despite many reports of positive findings from experiments conducted in vitro, in animal models
and in randomized controlled clinical trials, LLLT remains controversial. This likely is due to two main reasons;
firstly the biochemical mechanisms underlying the positive effects are incompletely understood, and secondly 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. In recent years major advances have been made in understanding the mechanisms that
operate at the cellular and tissue levels during LLLT. Mitochondria are thought to be the main site for the initial
effects of light and specifically cytochrome c oxidase that has absorption peaks in the red and near infrared regions
of the electromagnetic spectrum matches the action spectra of LLLT effects. The discovery that cells employ nitric
oxide (NO) synthesized in the mitochondria by neuronal nitric oxide synthase, to regulate respiration by competitive
binding to the oxygen binding of cytochrome c oxidase, now suggests how LLLT can affect cell metabolism. If
LLLT photodissociates inhibitory NO from cytochrome c oxidase, this would explain increased ATP production,
modulation of reactive oxygen species, reduction and prevention of apoptosis, stimulation of angiogenesis, increase
of blood flow and induction of transcription factors. In particular, signaling cascades are initiated via cyclic
adenosine monophosphate (cAMP) and nuclear factor kappa B (NF-&kgr;B). These signal transduction pathways in turn
lead to increased cell proliferation and migration (particularly by fibroblasts), modulation in levels of cytokines,
growth factors and inflammatory mediators, and increases in anti-apoptotic proteins. The results of these
biochemical and cellular changes in animals and patients include such benefits as increased healing in chronic
wounds, improvements in sports injuries and carpal tunnel syndrome, pain reduction in arthritis and neuropathies,
and amelioration of damage after heart attacks, stroke, nerve injury and retinal toxicity.
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