Name: Optimizing Photoneuromodulation Techniques to Evaluate the Role of Green Light-Emitting Diodes in Pain Management (Video) | JoVE Journal
Uploaded: 2025-03-28T14:30:00.000+00:00
Duration: 9 min 3 s
Description: Learn photoneuromodulation techniques using green light-emitting diodes for non-pharmacological pain management in preclinical and clinical studies. This method standardizes exposure protocols to improve research consistency.

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5 minutes

This research was supported by the Comprehensive Center for Pain and Addiction-University of Arizona (M.M.I., L.F.M.), the Anesthesiology Department at the University of Arizona (L.F.M.), and the Medical Scientist Training Program (MSTP) at the University of Arizona, College of Medicine, Tucson.

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Dr. Ibrahim has disclosed an outside interest in Luxxon Therapeutics to the University of Arizona. Conflicts of interest resulting from this interest are being managed by The University of Arizona in accordance with its policies. All other authors have no conflict of interest to report. None of the authors of the manuscript received any remuneration, reimbursement, or honorarium in any other manner. The authors are not affiliated with any vendor or pharmaceutical company associated with this study. None of this research, manuscript, or abstract has been previously presented and is not being considered for publication by any other journal.

Recent studies have explored the mechanisms underlying green light (GLED) analgesia13,21,22,23,24. However, further standardization of the methodology is needed to enhance its translation into clinical practice. The dose-dependent antinociceptive effects observed in preclinical models highlight the importance of optimizing exposure parameters to maximize thera...

Pharmacological treatments, particularly opioids, continue to be heavily relied upon for managing both acute and chronic pain conditions1. The effectiveness of pain management can be significantly affected by the frequency and severity of side effects associated with opioid use2. For this reason, a substantial amount of patients under opioid treatment do not achieve successful pain management3. Hence, pain physicians and the patient community are increasingly seeking non-pharmacological treatments that avoid the side effects associated with traditional pain medications. Photoneuromodulation has emerged as a promising solution and a safe therapy for managing pain.
Photoneuromodulation (PNM) is a non-invasive technique that uses light-emitting diodes (LED) to regulate biological processes4. Phototherapy was established thousands of years ago using sunlight, or heliotherapy, to treat skin conditions5. Subsequently, the concept of light influencing biological tissues has broadened, leading to the development of the photoneuromodulation term. PNM research is now expanding worldwide and has shown its effectiveness in a variety of clinical applications, including pain management6,7,8,9, improving sleep quality in patients with Alzheimer&#39;s disease10, and controlling depression11.
There is a growing emphasis on preclinical research and clinical trials aimed at investigating the mechanisms and therapeutic potential of photoneuromodulation for pain management. Among these approaches, green light-emitting diode therapy (GLED), using a 525 nm wavelength stimulation, has shown promising efficacy in reducing various types of pain, including migraines, fibromyalgia, and post-surgical pain12,13,14,15,16. Clinical trials have demonstrated that green light therapy consistently benefits patients suffering from migraine across multiple studies12,17,18, by reducing both headache pain and photophobia intensity during active migraine attacks19, as well as decreasing the frequency and duration of migraine episodes12. Preclinical studies also demonstrated that exposure to GLED can reverse thermal and mechanical hypersensitivity in a nerve injury model of neuropathic pain20. Further, preclinical studies have explored the mechanisms through which GLED influences pain perception and sensory thresholds13,21,22,23,24. These studies highlight the involvement of M-cones and the subsequent modulation of the ventral lateral geniculate nucleus (vLGN), which increases the activity of enkephalinergic neurons projecting to the dorsal raphe nucleus (DRN)22. Additional research has also emphasized the critical role of the rostral ventromedial medulla (RVM)21, a key regulator of descending pain modulation. Collectively, these findings suggest that GLED alters pain perception by modulating visual circuits that act on the descending pain pathways20,25. However, further research is required to facilitate its translation into clinical use.
In this article, we detail a comprehensive methodology for implementing GLED-based PNM, aiming to provide a reproducible framework for both experimental and clinical use. We describe the design and operation of GLED exposure, outline standardized application protocols, and discuss key considerations for ensuring efficacy and reproducibility. Additionally, we provide a detailed protocol for assessing the activity of both ascending and descending pain pathways, enabling a deeper investigation into their roles in modulating GLED-induced analgesia. By sharing this approach, we aim to advance research in non-pharmacological pain management and contribute to developing accessible, effective, and safer therapies.

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optimizing photoneuromodulation techniques to evaluate the role of green light-emitting diodes in pain management

Optimizing Photoneuromodulation Techniques to Evaluate the Role of Green Light-Emitting Diodes in Pain Management

Despite extensive research and the identification of numerous analgesic targets, the range of pharmacological treatments available for pain remains limited. However, a potential paradigm shift could introduce a new wave of non-pharmacological pain treatments with remarkable safety, efficacy, and tolerability. One promising area of investigation is photoneuromodulation using green light-emitting diodes (GLED, 525 nm), which have shown potential in alleviating pain in both acute and chronic conditions, leading to numerous preclinical and clinical studies exploring the efficacy of this therapy. These research projects have demonstrated how exposure to GLED enhances the activity of the endogenous opioid system in the brain and spinal cord after M-cone activation in the retina. The findings suggest that GLED may alleviate pain by modulating the descending pain pathway. In light of the compelling effects of GLED, the proliferation of photoneuromodulation investigations underscores the importance of establishing consistency in well-defined and standardized exposure protocols for preclinical and clinical trials. In preclinical studies, beneficial effects have been observed following a minimum of 2 days of exposure, with protocols involving 8 h of light at 100 lux during the 12 h light phase. In clinical trials, exposure protocols are tailored to the specific pathology under investigation. Exposure for 15 min has proven favorable in the modulation of acute post-surgical pain. For modulation of chronic pain, patients are instructed to use GLED at home for 1 to 2 h a day over 10 weeks. This article details preclinical and clinical protocols to improve reproducibility and consistency in the different studies evaluating photoneuromodulation benefits. By establishing these standardized protocols, this work aims to advance the clinical translation of GLED phototherapy as a viable non-pharmacological treatment for pain.

Greenlight exposure increases paw withdrawal latencies in a dose-dependent manner 
Figure 1A demonstrates that exposure to green light-emitting diodes (GLED) at various intensities (4, 50, 100, and 200 lux) significantly increased paw withdrawal latencies in a naïve rat model over a 7-day exposure period, indicating an antinociceptive effect of GLED. Baseline latencies before light exposure were comparable across groups. Starting from Day ...

Recent developments in pain research highlight the potential of photoneuromodulation using green light-emitting diodes (GLED) as a non-pharmacological treatment. GLED modulates pain pathways, offering effective pain relief. This article aims to standardize and refine GLED exposure protocols, improving consistency across studies and advancing the clinical application of this therapy.

Despite extensive research and the identification of numerous analgesic targets, the range of pharmacological treatments available for pain remains ...

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Learn photoneuromodulation techniques using green light-emitting diodes for non-pharmacological pain management in preclinical and clinical studies. This method standardizes exposure protocols to improve research consistency.

Optimizing Photoneuromodulation Techniques to Evaluate the Role of Green Light-Emitting Diodes in Pain Management

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