Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation

Laurent F. Martin, Aubin Moutal, Kevin Cheng, Stephanie M. Washington, Hugo Calligaro, Vasudha Goel, Tracy Kranz, Tally M. Largent-Milnes, Rajesh Khanna, Amol Patwardhan, Mohab M. Ibrahim

    Research output: Contribution to journalArticlepeer-review


    Benefits of phototherapy were characterized in multiple diseases including depression, circadian rhythm disruptions, and neurodegeneration. Studies on migraine and fibromyalgia patients revealed that green light-emitting diodes (GLED) exposure provides a pragmatic and safe therapy to manage chronic pain. In rodents, GLED reversed hypersensitivity related to neuropathic pain. However, little is known about the underlying mechanisms of GLED efficacy. Here, we sought to understand how green light modulates the endogenous opioid system. We first characterized how exposure to GLED stimulates release of β-endorphin and proenkephalin in the central nervous system of male rats. Moreover, by individually editing each of the receptors, we found that µ- and δ-opioid receptors are required for green light's antinociceptive effect in naïve rats and a model of HIV-induced peripheral neuropathy. We investigated how GLED could increase pain thresholds, and explored its potential in reversing hypersensitivity in a model of HIV-related neuropathy. Through behavioral and gene editing approaches, we identified that green light provides antinociception via modulation of the endogenous opioid system in the spinal cord. This work identifies a previously unknown mechanism by which GLED can improve pain management. Clinical translation of these results will advance the development of an innovative therapy devoid of adverse effects. Perspective: Development of new pain management therapies, especially for HIV patients, is crucial as long-term opioid prescription is not recommended due to adverse side effects. Green light addresses this necessity. Characterizing the underlying mechanisms of this potentially groundbreaking and safe antinociceptive therapy will advance its clinical translation.

    Original languageEnglish (US)
    Pages (from-to)1646-1656
    Number of pages11
    JournalJournal of Pain
    Issue number12
    StatePublished - Dec 2021


    • GP120
    • Phototherapy
    • endogenous opioids
    • green light
    • neuropathic pain

    ASJC Scopus subject areas

    • Neurology
    • Clinical Neurology
    • Anesthesiology and Pain Medicine


    Dive into the research topics of 'Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation'. Together they form a unique fingerprint.

    Cite this