Anju M. et al. - Photobiomodulation for diabetic peripheral neuropathy: a randomized controlled trial

In a randomized controlled trial comparing real laser treatment with a simulated laser, conducted among 200 people with diabetic peripheral neuropathy, ten days of photobiomodulation at 632.8 nm resulted in a significant change in the NSE and CGRP biomarkers, pain levels, and quality of life. NGF levels did not change, and this was a single randomized trial, not a meta-analysis: the level of evidence is not the same.

What this study measured

Diabetic peripheral neuropathy is a debilitating complication of long-term diabetes. The authors sought to determine whether blood-based neuronal biomarkers could reflect the effects of photobiomodulation.

Two hundred participants were randomized into two groups of one hundred. The intervention group received helium-neon laser photobiomodulation at 632.8 nm, at a reported dose of 3.1 J/cm², for 9 minutes on the dorsal and plantar surfaces of the foot, for ten days. The control group received a simulated laser, with assessments on day 0 and four weeks after treatment. Three serum biomarkers were measured: NSE, CGRP, and NGF. Clinical outcomes included the monofilament test, the biothesiometer, the Numerical Pain Rating Scale (NPRS), and a quality-of-life questionnaire.

Key Findings

The authors report significant variations in the intervention group, with one notable exception.

• 200 participants, 100 per group, simple-blind study comparing the treatment to a simulated laser
• Énolase spécifique du neurone (NSE) : p < 0,001
• Peptide lié au gène de la calcitonine (CGRP) : p < 0,001
• Nerve Growth Factor (NGF): no change, p = 0.937
• Score MNSI de neuropathie : p < 0,001
• Seuil de perception vibratoire (VPT) : p < 0,001
• Douleur à l’échelle numérique (NPRS) : p < 0,001
• Qualité de vie liée à la neuropathie : p < 0,001
• Parameters: 632.8 nm, 9 minutes, ten days

The abstract provides neither absolute values, nor confidence intervals, nor numerical comparisons between groups. The authors propose the NSE and the CGRP as indicators of treatment effect.

How Photobiomodulation Affects the Peripheral Nerves

The mechanisms are presented as hypotheses. Red light at 632.8 nm is thought to be absorbed by mitochondrial cytochrome c oxidase, which would increase ATP production. A reduction in oxidative stress and modulation of inflammatory pathways are also described, along with the hypothesis of an environment conducive to axonal regeneration. The absence of any change in NGF indicates that this hypothesis is not supported by the present findings.

Limits You Should Know

First and most important point: this is a single randomized trial, not a meta-analysis. An isolated result—even one involving 200 people—needs to be independently replicated and carries less weight than a synthesis of concordant trials.

It is important to note the negative result: NGF levels did not change (p = 0.937), even though it was the biomarker most closely associated with the hypothesis of nerve regeneration. The abstract presents the changes in the intervention group but does not provide those for the control group, which makes it impossible to quantify the benefit attributable to light. The blinding was simple, follow-up ended four weeks after treatment, and a change in a biomarker is not in itself a clinical benefit.

What This Means in Practice

This study supports further evaluation of photobiomodulation for this indication, but does not provide a basis for recommending it. For people with diabetes, glycemic control, foot care, and prescribed treatments remain the cornerstone of care. Any wound or loss of sensation in the foot warrants immediate medical evaluation.

Frequently Asked Questions

Does photobiomodulation reduce pain from diabetic neuropathy?

Le score de douleur (NPRS) a varié significativement dans le groupe interventionnel (p < 0,001), de même que la qualité de vie. Le résumé ne donne ni les valeurs avant et après, ni la comparaison avec le groupe témoin, donc l’ampleur réelle du soulagement reste inconnue.

What do the NSE, CGRP, and NGF biomarkers measure?

NSE is an enzyme released during neuronal damage; CGRP is a peptide involved in pain transmission; and NGF is a nerve growth factor. In this study, NSE and CGRP levels varied significantly, but NGF levels did not (p = 0.937).

Is a randomized trial involving 200 people sufficient to draw conclusions?

No. A sample size of 200 participants is substantial, but a single single-blind trial is no substitute for a meta-analysis of independent trials. The four-week follow-up period is short.

Reference

Anju M, Ummer Velladath S, Arun Maiya G, Hande M. A single-blind randomized controlled trial assessing the effect of photobiomodulation therapy on neuron-specific biomarkers in patients with type II diabetes mellitus and peripheral neuropathy. Diabetes Research and Clinical Practice, 2025. PMID 40090424. 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.