Advances in Low-Intensity Laser and Phototherapy (2010)

Ying-Ying Huang
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston MA; Department of
Dermatology, Harvard Medical School, Boston MA; Aesthetic and Plastic Center, Guangxi Medical
University, Nanning, Guangxi, P.R. ChinaAaron C.-H. Chen
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston MA; Boston University School of Medicine, Graduate Medical Sciences, Boston MA
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 MA26.1 Historical Introductions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 688
26.2 Cellular Chromophores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 688
26.3 LLLT and Signaling Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 692
26.4 Gene Transcription after LLLT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 695
26.5 Cellular Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 697
26.6 Tissue Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 700
26.7 Animal and Clinical Studies of LLLT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 701
26.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 706Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 706
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707The 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 tissue damage and death
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 noncoherent light. Despite many reports of positive
findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, low level light therapy (LLLT) remains controversial. This controversy is likely due to
two main reasons; first, the biochemical mechanisms underlying the positive effects are incompletely understood, and second, the complexity of rationally choosing among 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
particular, a biphasic dose response has been frequently observed where low levels of light have a
much better effect than higher levels. This chapter will cover some of the proposed cellular chromophores responsible for the effect of visible light on mammalian cells, including cytochrome c
oxidase (with absorption peaks in the near infrared region of the spectrum) and photoactive porphyrins and flavins. Mitochondria are thought to be a likely site for the initial effects of light and
the involvement of nitric oxide had been postulated. Activation of the respiratory chain leads toof Photonics for Biomedicalincreased ATP production, modulation of reactive oxygen species, and activation of transcription
factors. These effects in turn lead to increased cell proliferation and migration (particularly by
fibroblasts), modulation in levels of cytokines, growth factors and inflammatory mediators, prevention of cell death by anti-apoptotic signaling, and increased tissue oxygenation. 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.