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

Summary

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.

Abstract

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.

Introduction

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 em....

Protocol

All animal procedures were approved by the Institutional Animal Care and Use Committee of the University of Arizona and conform to the guidelines for using laboratory animals of the National Institutes of Health. Pathogen-free, adult Sprague Dawley rats (weight at testing: 275-330 g) were housed in standard vivarium rat cages (3 rats per cage) in climate-controlled rooms on a 12-hour light/dark cycle and were allowed ad lib access to food and water. All behavioral experiments were conducted by experimenters blinded to the treatment conditions. All human procedures received approval from the University of Arizona Institutional Review Board (IRB) under protocol number (....

Results

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 fr.......

Discussion

Recent studies have explored the mechanisms underlying green light (GLED) analgesia^{13,21,22,23,24}. 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.......

Materials

Name	Company	Catalog Number	Comments
24 h Mechanical mini timer for LED strips	bn-link	BND-60/U47	https://www.bn-link.com/products/bn-link-indoor-24-hour-mechanical-outlet-timer-3-prong-2-pack?variant=42704897245237&currency= USD&utm_medium=product_sync& utm_source=google&utm_content= sag_organic& utm_campaign= sag_organic&gad_source=1& gclid=Cj0KCQjwurS3BhCGARI sADdUH50dy8sYj4Ku2ZmM14-3Yp3iajSY 4TgRze8UvSuyhq81-h 1E6GChOXgaAhwYEALw_wcB
AC 5050 SMD LED Tape Rope Strip Lighting	LED Supply Co	LS-AC50-GR	https://www.ledsupply.com/led-strips/ac-power-5050-led-strips Green Strip Lighting for all exposure rooms 120V AC, 60Hz
AC 5050 SMD LED Tape Rope Strip Lighting	LED Supply Co	LS-AC50-WH	https://www.ledsupply.com/led-strips/ac-power-5050-led-strips White Strip Lighting for all exposure rooms 120V AC, 60Hz
Allodynia Software	National Instruments, LabView 2015		https://www.ni.com/en-us/shop/product/labview.html
Amazon Basics Lightweight Super Soft Easy Care Microfiber 4-Piece Bed Sheet Set with 14-Inch Deep Pockets, Queen, Black, Solid	Amazon Basics Store		Amazon.com: Amazon Basics Lightweight Super Soft Easy Care Microfiber 4-Piece Bed Sheet Set with 14-Inch Deep Pockets, Queen, Black, Solid : Amazon Basics: Home & Kitchen
Computerized Pressure Pain Algometer	Medoc advanced medical systems	ID 00186	https://www.medoc-web.com/algomed
Digital Lux Meter	Edmund Optics	52270	https://www.edmundoptics.com/
Elevated metal mesh stand for Von Frey	Bioseb	BIO-STD2-EVF	https://www.bioseb.com/en/pain-mechanical-allodynia_hyperalgesia/1689-elevated-metal_mesh-stand-30-cm-height-to-fit-up_to-2-pvf-cages.html
Fisherbrand Thermometers	Fischer Scientific	13-201-577	https://www.fishersci.com/shop/products/fisherbrand-10-30-ground-joint-thermometers-6/13201927
Medline Autoclavable Plastic Washbasins	Truway Health	42141606	https://truwayhealth.com/medline-autoclavable-plastic-washbasins/?cmp_id=21122060336&adg_id= &kwd=&device=c& gad_source=1&gclid= CjwKCAjw0aS3BhA3EiwAKaD2ZTHY8_ 7W__ gXC7Wf3Kv3jJa6KQrNI-4JrdYqKM9IO v8moeW6ylEpzRoCnZ8QAvD_BwE
Modular holder cages for rats and mice	Bioseb	BIO-PVF	https://bioseb.com/en/pain-mechanical-allodynia-hyperalgesia/1206-modular-holder-cages-for-rats-and-mice.html
Plantar Test for Thermal Stimulation - Hargreaves Apparatus	Ugo Basile	37570	https://ugobasile.com/products/categories/pain-and-inflammation/plantar-test-for-thermal-stimulation includes semi-transparent glass panel and individual animal enclosures for 6 rats/12 mice
Scotch 700 Electrical Tape, 3/4 in. x 66 ft. x 0.007 in.	3M		https://www.3m.com/3M/en_US/p/d/cbgnawus1596/
Touch Test Sensory Evaluators (von Frey Filaments)	North Coast Medical and Rehabilitation Products	NC12775-99	https://www.ncmedical.com/products/touch-test-sensory-evaluators_1278.html
Touch Test Sensory Evaluators (von Frey Filaments)	North Coast Medical and Rehabilitation Products	NC12775-20	https://www.ncmedical.com/products/touch-test-sensory-evaluators_1278.html
TRINITY EcoStorage 5-Tier , 48 x 24 x 72, Commercial Wire Shelving	Trinity	952471	https://trinityii.com/ecostorage-5-tier-48x24x72-wire-shelving-nsf-with-wheels-chrome/