BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY
The 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 cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, low level light therapy remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and 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.
A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in low level light therapy, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.
1. INTRODUCTION
1.1. Brief history
Low level light therapy (LLLT) is the application of light (usually a low power laser or LED in the range of 1mW – 500mW) to a pathology to promote tissue regeneration, reduce inflammation and relieve pain. The light is typically of narrow spectral width in the red or near infrared
(NIR) spectrum (600nm – 1000nm), with a power density (irradiance) between 1mw-5W/cm . It is typically applied to the injury for a minute or so, a few times a week for several weeks. Unlike other medical laser pro- cedures, LLLT is not an ablative or thermal mechanism, but rather a pho- tochemical effect comparable to photosynthesis in plants whereby the light is absorbed and exerts a chemical change.
The phenomenon was first published by Endre Mester at Semmelweis University, Budapest, Hungary in 1967 a few years after the first working laser was invented (Mester et al. 1967). Mester conducted an experiment to test if laser radiation might cause cancer in mice. He shaved the hair off their backs, divided them into two groups and irradiated one group with a low powered ruby laser (694-nm). The treatment group did not get cancer and to his surprise, the hair grew back more quickly than the untreated group. He called this “Laser Biostimulation”.
1.2. Evidence for effectiveness of LLLT
Since 1967 over 100 phase III, randomized, double-blind, placebo- controlled, clinical trials (RCTs) have been published and supported by over 1,000 laboratory studies investigating the primary mechanisms and the cascade of secondary effects that contribute to a range of local tissue and systemic effects.
RCTs with positive outcomes have been published on pathologies as diverse as osteoarthritis (Bertolucci and Grey 1995; Ozdemir et al. 2001; Stelian et al. 1992), tendonopathies (Bjordal et al. 2006b; Stergioulas et al. 2008; Vasseljen et al. 1992), wounds (Caetano et al. 2009; Gupta et al. 1998; Ozcelik et al. 2008; Schubert et al. 2007), back pain (Basford et al. 1999), neck pain (Chow et al. 2006; Gur et al. 2004), muscle fatigue (Leal Junior et al. 2008a; Leal Junior et al. 2008b), peripheral nerve injuries (Rochkind et al. 2007) and strokes (Lampl et al. 2007; Zivin et al. 2009); nevertheless results have not always been positive. This failure in certain circumstances can be attributed to several factors including dosimetry (inadequate or too much energy delivered, inadequate or too much irradiance, inap- propriate pulse structure, irradiation of insufficient area of the pathology), inappropriate anatomical treatment location and concurrent patient medication (such as steroidal and non-steroidal anti-inflammatories which can inhibit healing) (Aimbire et al. 2006; Goncalves et al. 2007).
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Credit to
Ying-Ying Huang Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Department of Dermatology, Harvard Medical School, Boston, MA; Aesthetic and Plastic Center of Guangxi Medical University, Nanning, P.R. China
Aaron C.-H. Chen Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Boston University School of Medicine, Graduate Medical Sciences, Boston, MA
James D. Carroll THOR Photomedicine Ltd, 18A East Street, Chesham, HP5 1HQ, UK
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, MA
