Hamblin, M.R. - Photobiomodulation and Anti-Inflammatory Effects: A Review of the Mechanisms

This publication is a review of the mechanisms of photobiomodulation, not a clinical trial. It describes how the absorption of red and near-infrared light by cellular chromophores appears to lead to a reduction in inflammation in numerous experimental models.

What This Publication Examines

This review focuses on the anti-inflammatory effects of photobiomodulation, also known as low-intensity laser therapy. It is important to note that this is neither a clinical trial nor a meta-analysis. No patients were randomized, and no clinical outcomes were measured in this study. The author puts the results from cellular studies and animal models into perspective.

The question at hand concerns the mechanism: through what sequence of events can red or near-infrared light applied to tissue modify an inflammatory response? The review offers a three-tiered analysis, ranging from the initial chromophores to gene expression.

Key points identified

The author structures his review around a three-stage cascade, followed by a series of experimental observations.

• Primary chromophores identified: mitochondrial cytochrome c oxidase and calcium channels, which are believed to be activated through the absorption of light by opsins
• Side effects of photon absorption: increased ATP levels, a brief surge in reactive oxygen species, increased nitric oxide levels, and modulation of calcium levels
• Tertiary effects: activation of a wide range of transcription factors, improved cell survival, increased proliferation and migration, and synthesis of new proteins
• A pronounced, biphasic dose-response relationship: low light levels have a stimulating effect, while high light levels have an inhibitory effect
• State-dependent effect: production of reactive oxygen species in normal cells, but a decrease in these same levels in cells under oxidative stress and in animal models of disease
• NF-κB is activated in normal, quiescent cells, whereas inflammatory markers decrease in activated, inflammatory cells
• A reduction in M1 phenotype markers in activated macrophages, along with decreased levels of reactive nitrogen species and prostaglandins, has been reported in various animal models

The author presents the overall reduction in inflammation as one of the most reproducible effects of photobiomodulation, citing joint disorders, trauma, lung damage, the brain, abdominal adipose tissue, wounds, and the spinal cord.

How Photobiomodulation May Affect Inflammation

The underlying principle is as follows: light is absorbed by a target molecule, which alters energy metabolism and cellular signaling, and subsequently the gene expression profile. The key feature highlighted is the context-dependent nature of the response: the same light parameter does not produce the same result depending on whether the cell is at rest or already engaged in an inflammatory response. This context-dependence, combined with the biphasic response, may explain the variability in experimental results.

Limits You Should Know

The first limitation stems from the nature of the document: a review of mechanisms does not demonstrate a clinical benefit. The reported findings are derived primarily from cellular and animal studies, and their applicability to humans has not been established. The text provides neither effect sizes, confidence intervals, nor an aggregate effect estimate.

The biphasic response itself poses a practical limitation: a dose that is too high may inhibit rather than stimulate. Finally, this review was published in 2017; more recent studies have been published since then, and the recommended parameters may have changed.

What This Means in Practice

This publication serves as a framework for interpreting clinical trials, not as evidence of efficacy. It helps explain why two similar protocols sometimes yield different results, and why dosage is critical. It does not allow for any conclusions regarding a specific indication in humans.

Frequently Asked Questions

Does this study prove that photobiomodulation reduces inflammation in humans?

No. It is a review of mechanisms based on cellular and animal studies. It describes plausible pathways, but does not measure any clinical outcomes in patients and does not replace randomized trials.

Why do we refer to a biphasic response?

This is because, according to this journal, low levels of light have a stimulating effect, while high levels have an inhibitory effect. Increasing the dose therefore does not necessarily enhance the desired effect; in fact, it may eliminate it.

What is the role of cytochrome c oxidase?

It is the primary chromophore identified in mitochondria, along with calcium channels. Its activation by light is thought to cause an increase in ATP and nitric oxide, as well as a brief surge in reactive oxygen species.

Reference

Hamblin, M.R. “Mechanisms and Applications of the Anti-Inflammatory Effects of Photobiomodulation.” AIMS Biophysics, 2017. PMID 28748217. View the study on PubMed

This summary is provided for informational purposes only and does not constitute medical advice. Photobiomodulation is not a substitute for prescribed treatment. Consult a healthcare professional.