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As recently suggested [16], it is unreasonable to expect that a single light dose will have a universal application. However, many wavelengths may be efficacious for treatment of nerve injury if the wavelength can penetrate to the target tissue and the parameters used are optimized so that a therapeutic dose of light is applied. For the majority of PBM studies, dose parameters reported were values delivered to the skin surface and not what was actually delivered to the target tissue. Our laboratory was the first to measure light penetration in an anesthetized rat from the dermis to the depth of the spinal [http://www.selleckchem.com/products/scr7.html SCR7] cord using a smart, tissue-activated optical fiber probe attached to a spectrophotometer [17]. We also investigated the effect of PBM on peripheral nerve regeneration and function after severe median nerve injury and microsurgical autologous nerve graft repair using fibrin glue [18]. For these experiments, the percentage of output power of an 810?nm wavelength laser transcutaneously transmitted to the depth of the median nerve was measured in an anesthetized rat. Power transmitted through the skin to the depth of the nerve was 47% of the output power. Based on these measurements, laser parameters were chosen so that a power density of 10?mW/cm2 was achieved at the depth of the nerve. Laser [http://en.wikipedia.org/wiki/Mianserin Mianserin HCl] treatment with these parameters resulted in faster functional recovery of grip strength (P?[http://www.selleckchem.com/products/MS-275.html Entinostat in vivo] penetration experiments of 980?nm wavelength light revealed that approximately 2.45% (average of 4.0?W and 1.0?W measurement) of the light penetrated to the level of the peroneal nerve. The total energy delivered on the skin surface was calculated to be 65?J. Two different output powers (2 and 4?W) were used for the pilot study. Although the total energy was kept at 65?J for both groups, nerve regeneration was significantly better with the 2?W laser treatment compared to the control while regeneration of the injured nerves was inhibited when treated with 4?W. Therefore, both energy density (200?mJ/cm2) and power density (10?mW/cm2) were considered for refining the calculation for the long-term study. Based on the toe spread reflex, these laser treatment parameters promoted an earlier and faster nerve regeneration and functional recovery compared to the non-treated controls and supported nerve regeneration and reinnervation of the involved muscles by 9 weeks post-injury.