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Dose-Response, 9:602–618, 2011 Formerly Nonlinearity in Biology, Toxicology, and Medicine Copyright © 2011 University of Massachusetts ISSN: 1559-3258 DOI: 10.2203/dose-response.11-009.Hamblin BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY – AN UPDATE Ying-Ying Huang Wellman Center for Photomedicine, Massachusetts General Hospital; Department of Dermatology, Harvard Medical School, Boston MA; and Aesthetic and Plastic Center of Guangxi Medical University, China Sulbha K Sharma Wellman Center for Photomedicine, Massachusetts General Hospital James Carroll THOR Photomedicine Ltd, UK Michael R Hamblin Wellman Center for Photomedicine, Massachusetts General Hospital; Department of Dermatology, Harvard Medical School; Harvard- MIT Division of Health Sciences and Technology Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose- response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in ani- mal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mito- chondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurologi- cal effects observed when the number of treatments is varied, and when the energy den- sity of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments. Keywords: low level laser therapy, photobiomodulation, biphasic dose response, reactive oxygen species, nitric oxide, traumatic brain injury INTRODUCTION Low level laser (light) therapy (LLLT) employs visible (generally red) or near-infrared light generated from a laser or light emitting diode (LED) system to treat diverse injuries or pathologies in humans or ani- mals. The light is typically of narrow spectral width between 600nm - 1000nm. The fluence (energy density) used is generally between 1 and 20 J/cm2 while the irradiance (power density) can vary widely depending on Address correspondence to Prof. Michael R. Hamblin, BAR414, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114; Ph: 617-726-6182; Fax:617-726-8566; email: Hamblin@helix.mgh.har vard.edu 602PDF Image | BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY AN UPDATE
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