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Green Light Exposure Elicits Anti-inflammation, Endogenous Opioid Release and Dampens Synaptic Potentiation to Relieve Post-surgical Pain

  • Laurent F. Martin
    Affiliations
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona

    Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Kevin Cheng
    Affiliations
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Stephanie M. Washington
    Affiliations
    Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Millie Denton
    Affiliations
    Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Vasudha Goel
    Affiliations
    Department of Anesthesiology, The University of Minnesota Medical School, Minneapolis, Minnesota
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  • Maithili Khandekar
    Affiliations
    Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Tally M. Largent-Milnes
    Affiliations
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona
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  • Amol Patwardhan
    Affiliations
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona

    Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson, Arizona

    Department of Neurosurgery, College of Medicine, The University of Arizona, Tucson, Arizona

    Comprehensive Pain and Addiction Center, The University of Arizona, Tucson, Arizona
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  • Mohab M. Ibrahim
    Correspondence
    Address reprint requests to Mohab M. Ibrahim, MD, PhD, Department of Anesthesiology, College of Medicine, University of Arizona, 1501 North Campbell Drive, P.O. Box 245050, Tucson, AZ 85724
    Affiliations
    Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona

    Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson, Arizona

    Department of Neurosurgery, College of Medicine, The University of Arizona, Tucson, Arizona

    Comprehensive Pain and Addiction Center, The University of Arizona, Tucson, Arizona
    Search for articles by this author
Published:October 22, 2022DOI:https://doi.org/10.1016/j.jpain.2022.10.011

      Highlights

      • Green light (GLED) potentiates ibuprofen- and morphine-induced antinociception
      • GLED exposure reduces the required morphine dose to achieve antinociception
      • Spinal neuroinflammation is reduced after GLED exposure
      • GLED exposure decreases dorsal horn glutamatergic receptor expression

      Abstract

      Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents. However, its underlying mechanisms remain incompletely defined. In this study, we demonstrate that green light exposure reduced postsurgical hypersensitivity in rats. Moreover, this therapy potentiated the antinociceptive effects of morphine and ibuprofen on mechanical allodynia in male rats. Importantly, in female rats, GLED potentiated the antinociceptive effects of morphine but did not affect that of ibuprofen. We showed that green light increases endogenous opioid levels while lessening synaptic plasticity and neuroinflammation. Importantly, this study reveals new insights into how light exposure can affect neuroinflammation and plasticity in both genders. Clinical translation of these results could provide patients with improved pain control and decrease opioid consumption. Given the noninvasive nature of green light, this innovative therapy would be readily implementable in hospitals.
      Perspective: This study provides a potential additional therapy to decrease postsurgical pain. Given the safety, availability, and the efficacy of green light therapy, there is a significant potential for advancing the green light therapy to clinical trials and eventual translation to clinical settings.

      Graphical abstract

      Key words

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