This conclusion rests partly on four assumptions: 1) ‘a delayed analgesic response does not seem plausible’; 2) ‘the included trials investigated similar treatment and dosing protocols’; 3) ‘results varied from exceptionally

effective to slightly harmful’; and 4) ‘conflicting results are difficult to explain’. First, the conflicting results in LLLT were explained recently in our neck pain review with 16 LLLT trials included (Chow et al 2009), where we found significant short-term pain relief at 19.4 mm (95% CI 9.7 to 29.2). In the current review, www.selleckchem.com/products/BAY-73-4506.html two studies with 830 nm wavelengths used an extremely high dose of 54 Joules (Dundar et al 2007) and a very low dose of 0.9 Joules (Thorsen et al 1992), respectively. In our review, we found that an optimal dose was 5.9 Joules per point for this wavelength. The World Association for Laser Therapy (WALT) developed evidence-based guidelines with wavelength-specific doses and treatment protocols in 2005 (www.walt.nu/dosage-recommendations.html).

The WALT recommendation is to use a minimum 4 Joules at each of a minimum of four points in the cervical spine with 830 nm wavelength. The reviewers build the case that a pattern of delayed response did not appear consistently within trials measuring at different time-points. This statement is contradicted by the results in trials measuring MK-2206 in vivo at several time-points. One trial found no significant effect after 2 weeks of daily LLLT, but a significant delayed analgesic response at 14 weeks follow-up (Altan et al 2003). Another included trial reported a delayed analgesic response with a mean reduction in pain intensity of 10 mm over placebo (Gur et al 2004) from the end of LLLT until the one week follow-up. The last study with medium-term follow-up reported pain intensity to be as low as 9.46 mm (+/– 13.17) after LLLT, thus leaving no possibility to investigate possible delayed analgesic responses to LLLT (Ceccherelli et al 1989). Evidence of delayed analgesic responses

after intensive Rutecarpine regimens of LLLT has been reported for other diagnoses, too (Vasseljen et al 1992, Bjordal, 2007). For these reasons, the inclusion of a crossover trial (Thorsen et al 1992) in meta-analyses is not valid. The crossover trial was also interpreted as ‘slightly harmful’, although the original trial report dismissed this as an artefact caused by baseline imbalance after an exploratory statistical analysis. Balancing benefit and harm is always an important issue when drugs are concerned. We believe that the authors fail to address this issue properly when concluding that a combination drug (orphenadrine/paracetamol) is effective in the short-term. The actual drug branded as ‘Norgesic’ was only investigated in a single Norwegian trial lasting one week with no follow-up.