Mechanisms and applications of the anti-inflammatory effects of photobiomodulation

Abstract

Photobiomodulation (PBM) also known as low-level level laser therapy is the use of red and near-infrared light to stimulate healing, relieve pain, and reduce inflammation. The primary chromophores have been identified as cytochrome c oxidase in mitochondria, and calcium ion channels (possibly mediated by light absorption by opsins). Secondary effects of photon absorption include increases in ATP, a brief burst of reactive oxygen species, an increase in nitric oxide, and modulation of calcium levels. Tertiary effects include activation of a wide range of transcription factors leading to improved cell survival, increased proliferation and migration, and new protein synthesis. There is a pronounced biphasic dose response whereby low levels of light have stimulating effects, while high levels of light have inhibitory effects. It has been found that PBM can produce ROS in normal cells, but when used in oxidatively stressed cells or in animal models of disease, ROS levels are lowered. PBM is able to up-regulate anti-oxidant defenses and reduce oxidative stress. It was shown that PBM can activate NF-kB in normal quiescent cells, however in activated inflammatory cells, inflammatory markers were decreased. One of the most reproducible effects of PBM is an overall reduction in inflammation, which is particularly important for disorders of the joints, traumatic injuries, lung disorders, and in the brain. PBM has been shown to reduce markers of M1 phenotype in activated macrophages. Many reports have shown reductions in reactive nitrogen species and prostaglandins in various animal models. PBM can reduce inflammation in the brain, abdominal fat, wounds, lungs, spinal cord.

Keywords: animal studies; chromophores; clinical trials; inflammation; low-level laser therapy; photobiomodulation.

Figure 1

Chromophores in PBM. Cytochrome c oxidase in respiratory chain absorbs mainly red (and NIR) light by heme and copper; Heat-gated TRP ion channels absorb NIR (and blue light) via structured water; opsins absorb mainly blue/green light via cis-retinal; flavoproteins and cryptochromes absorb mainly blue light via pterin.

Figure 2

NFkB is activated by PBM induced ROS in embryonic fibroblasts. (A) Intracellular ROS measured by DCDHF fluorescence; (B) NF-kB activation measured by a luciferase assay; (C) NF-kB activation is inhibited by antioxidants; (D) ATP increase is not affected by antioxidants. Figure adapted from data in [34].

Figure 3

Dose response of 810 nm laser in cortical neurons. (A) ATP production as a function of fluence; (B) Mitochondrial membrane potential (JC1 red/green ratio); (C) Mitochondrial ROS. Figure adapted from data in [35].

Figure 4

PBM reduces oxidative stress in cortical neurons. Oxidative stress was induced by three different treatments (cobalt chloride, hydrogen peroxide, rotenone) and cells were treated with 3 J/cm² 810 nm. (A) Mitochondrial ROS, (B) Mitochondrial membrane potential (tetramethylrhodamine methyl ester). Figure adapted from data in [39].

Figure 5

PBM reduces inflammatory markers in activated murine DCs in vitro. (A) Flow cytometry was used to measure MHC class II, CD86, CD11c (dexamethasone was used as positive control); (B) Secreted IL12 measured by ELISA. Figure adapted from data in [44].

Figure 6

Animal models in which the anti-inflammatory effects of PBM have been shown. Acute traumatic brain injury; experimental autoimmune encephalomyelitis; spinal cord injury; wound healing; muscle exercise and recovery; inflammatory pain in paw; abdominal fat; lung inflammation; knee arthritis.

Figure 7

Human clinical indications concentrating on anti-inflammatory effects. Autoimmune thyroiditis; muscle exercise and recovery; Achilles tendinopathy; knee arthritis; psoriasis; alopecia areata.