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.