Low-Level Laser Therapy (LLLT)

Low-level lasers have been proposed as early as 1967 by Pr. Endre Mester, in Semmel – weis University Budapest, Hungary. Forty years later, there is still much debate about the role LLLT plays in wound healing.

19.2.1 Photomodulation

Photomodulation (a term very often proposed by the authors of papers on LLLT, but for which a clear definition is missing) by light in the red to near infrared (630-1000 nm) is supposed to be the key mechanism to accelerate wound healing. Photomodulation would augment recovery pathways promoting cellular viability, and restoring cellular function following injury. Since photomodulation involves the absorption of a specific wavelength of light by the photoaceptor molecule, two questions remain open: (i) which are the photo­acceptors? (ii) which are the action spectra?

It has been postulated that the mechanism of photomodulation at the cellular level is based on the absorption of monochromatic visible and NIR radiation by components of the cellular respiratory chain. Absorption and promotion of electronically excited states cause changes in redox properties of these molecules, and acceleration of electron transfer (pri­mary reactions). Primary reactions in mitochondria of eukaryotic cells are supposed to be followed by a cascade of secondary reactions (photosignal transduction and amplification chain or cellular signaling) occurring in cell cytoplasm, membrane, and nucleus [2]. Cyto­chrome c oxidase would be a key photoacceptor of light in the far-red to near-IR spectral range. Photostimulation would induce a cascade of signaling events initiated by the initial absorption of light by cytochrome oxidase. These signaling events may include the activa­tion of immediate early genes, transcription factors, cytochrome oxidase subunit gene expression, and a host of other enzymes and pathways related to increased oxidative metab­olism [3,4]. It has also been suggested that activation of the respiratory chain by irradiation would increase production of superoxide anions [5] . However, depending on the light dose some of these mechanisms can prevail significantly. Experiments with E. coli provided evidence that, at different light doses, different mechanisms were responsible (Fig. 19.2): a photochemical one at low doses, and a thermal one at higher doses [6]. In the event of

the photoaccepetors being located in the mitochondria, Fig. 19.2 suggests three regulation pathways.

The first one is the control of the photoacceptor over the level of intracellular ATP. It is a well-known fact that even small changes in the ATP level can significantly alter cellular metabolism. The second and third regulation pathways are mediated through the cellular redox state. This may involve redox-sensitive transcription factors (NF-kB and AP-1 in Fig. 19.3), or cellular signaling homeostatic cascades from cytoplasm via the cell mem­brane to nucleus [7].

In the context of wound healing, only a few studies were initiated to determine the optimal action spectra (or the optimal wavelength). For example, Reedy performed a wound-healing evaluation in diabetic rats using two different wavelengths (He_Ne laser: 632.8 nm) and (Ga-As laser diode: 904 nm) using similar parameters : 7 mW-1 J/cm2. Although the results indicated that both the He-Ne and Ga-As lasers enhanced the repair of healing-impaired wounds in diabetic rats compared to the controls, the magnitude of the effects differed con­siderably between the two lasers. The findings from the biomechanical and biochemical anal­ysis of healed diabetic wounds demonstrated that the He-Ne laser was superior to the Ga-As laser in promoting wound repair. Further, the He-Ne laser produced greater healing effects than the Ga-As laser, with the same energy density. The differences between the He-Ne and Ga-As lasers in promoting wound repair in diabetic rats are attributed to their photochemical interaction with the cells. Evidence suggests that the absorption of light emitted by He-Ne laser at 632.8 nm initiates with the components of respiratory chain, whereas radiation emit­ted by the Ga-As laser at 904 nm begins at the membrane level, that is, during the cascade of molecular events that leads to photochemical response of the tissue [8].