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Y.-Y. Huang and others had three treatments (one treatment, three consecutive days), each treat- ment was with a different laser or placebo. The study was properly blind- ed and randomized. There was a significant difference in skin tempera- ture of the forehead and in recorded pain scores. The greatest improve- ments were for the 150mW laser (Hashimoto et al. 1997). There have been several systematic reviews and meta analyses of RCTs and these have revealed some irradiance dependant effects: Bjordal pub- lished a review of LLLT for chronic joint disorders and identified 14 RCTs of suitable methodological quality, 4 of which failed to report a significant effect because the irradiance was either too high or too low, and/or deliv- ered insufficient energy, the remaining eight studies all produced positive effects (Bjordal et al. 2003). Tumilty reviewed 25 LLLT RCTs of tendinopathies,13 of which (55%) failed to produce a positive outcome, all of these negative/inconclusive studies that recorded irradiance (or could subsequently be established) had delivered an irradiance in excess of the guidelines set by the World Association for Laser Therapy (www.walt.nu) (Tumilty et al. 2009). 3.3. Biphasic Response—time or energy density Again, Peter Bolton’s study mentioned in 3.2 above had an energy density aspect showing a different response for each of the irradiances used. For the 400mW/cm2 study he found increasing energy density from 2.4 J/cm2 to 7.2 J/cm2 increased fibroblast proliferation, in the 800 mW/cm2 group increasing energy density from 2.4 J/cm2 to 7.2 J/cm2 decreased fibroblast proliferation (Bolton et al. 1991). Anders’ study also mentioned in 3.2 above looked at four energy density groups, and for the irradiance parameters that produced significant results increasing energy density increased neurite length (Anders et al. 2007) Table 3. Yamaura and colleagues found a biphasic dose response in MTT activity in rheumatoid arthritis synoviocytes after 810-nm laser with a peak at 8 J/cm2 and less effect at lower and higher fluences (Yamaura et al. 2009). Loevschall meas- ured human oral mucosal fibroblast cell proliferation by incorporation of tritiated thymidine after varying fluences of 812-nm laser delivered at 4.5 mW/cm2 and found a biphasic dose response with a distinct peak at 0.45 J/cm2 (Loevschall and Arenholt-Bindslev 1994). Another study (al-Watban and Andres 2001) looked at chinese hamster ovary and human fibroblast proliferation after various fluences of He-Ne laser delivered at a constant irradiance of 1.25 mW/cm2. Again they found a clear biphasic dose response with a peak at 0.18 J/cm2. Zhang et al (Zhang et al. 2003) found a biphasic dose response in human fibroblast cell numbers after treatment with varying fluences of 628-nm light, with a maximum increase of 30% after 0.88 J/cm2 and an actual reduction appearing at 9 J/cm2. Brondon and colleagues (Brondon et al. 2005) found that two treatments per dayPDF Image | BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY
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