Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

Abstract

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.

Photobiomodulation of human adipose-derived stem cells using 810 nm and 980 nm lasers operates via different mechanisms of action

“…There have been many different molecules that have been proposed over the years to act as the primary photoacceptor or chromophore in PBM [3]. The first law of photobiology states that a photon must be absorbed by a specific chromophore located inside cells or tissues to have any biological effect.…”

Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As) Augments Dermal Wound Healing in Immunosuppressed Rats

“…Therefore, recent extensive research have focused on enhancing the repair process through strategies including the application of tissue engineered scaffolds, gene therapy, stem cell-based therapy and biophysical therapeutic intervention using light-based modality (photobiomodulation, PBM or low-level laser/light therapy, LLLT) that can promote the healing process and save patients from amputation and other severe complications [2,9–12]. So far, the therapies available for wound repair in immunosuppressed subjects are less effective and this has promoted us to consider about PBM therapy for effectual chronic wound care management.…”

“…It has been reported that cytochrome c oxidase (CCO) is a primary photoacceptor of red and near-infrared (NIR) radiation in mitochondria of cells that activates retrograde light-sensitive cellular signaling events to transport the light signal from mitochondria to nucleus, which eventually alter the cellular metabolism and functions [15]. Both scattering and absorption of light by tissue are highly wavelength-dependent and NIR light around 810–830 nm have been found to have the deepest penetration and homogeneous illumination of the full dermis and part of the hypodermis [12,15]. …”

“…In another study, it has been clearly shown that 830 nm light can potentially restore the potassium cyanide-inactivated CCO function [23]. The aforementioned findings had encouraged us to design the present study using 810 nm laser, because of its good penetration in tissues and the capacity of this wavelength change the biological signalization of genes and physiological responses, like tissue repair, inflammation and pain control among other responses [12,24,25]. …”

A novel treatment for chronic opioid use after surgery

“…The proposed mechanism of action of laser therapy relates to the ability of damaged cells to absorb the emitted photons and transform the energy into adenosine triphosphate (ATP). Laser stimulation enhances the production of ATP by forming singlet oxygen and reactive oxygen species [15]. The lightabsorbing components of the cell are termed chromophores or photoacceptors and are contained within the mitochondria and cellular membrane.…”