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Mechanisms and Pathways of Pain Photobiomodulation: A Narrative Review

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

    Department of Anesthesiology, College of Medicine, University of Arizona, Tucson, Arizona
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  • Marvin J. Slepian
    Affiliations
    Department of Medicine, College of Medicine, University of Arizona, Tucson, Arizona

    Department of Biomedical Engineering, University of Arizona, Tucson, Arizona

    Sarver Heart Center, University of Arizona, Tucson, Arizona

    Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, Arizona
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  • Amol M. Patwardhan
    Affiliations
    Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona

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

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

    Comprehensive Pain and Addiction Center, 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 Dr, PO Box 245050, Tucson, AZ 85724. Tel: (520) 626-4281; Fax: (520) 626-2204.
    Affiliations
    Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona

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

    Department of Neurosurgery, College of Medicine, University of Arizona, Tucson, Arizona
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Published:February 23, 2021DOI:https://doi.org/10.1016/j.jpain.2021.02.005

      Highlights

      • Light provides analgesia through cutaneous application or visual stimulation.
      • Depending on wavelengths, visual stimuli may induce analgesia or hypersensitivity.
      • Light-induced analgesia relies on both central and peripheral mechanisms.
      • ipRGCs, RVM, and inflammation play a crucial role in phototherapy pain management.
      • Phototherapy for pain management is efficacious with scarce side effects.

      Abstract

      A growing body of evidence supports the modulation of pain by light exposure. As such, phototherapy is being increasingly utilized for the management of a variety of pain conditions. The modes of delivery, and hence applications of phototherapy, vary by wavelength, intensity, and route of exposure. As such, differing mechanisms of action exist depending upon those parameters. Cutaneous application of red light (660 nm) has been shown to reduce pain in neuropathies and complex regional pain syndrome-I, whereas visual application of the same wavelength of red light has been reported to exacerbate migraine headache in patients and lead to the development of functional pain in animal models. Interestingly visual exposure to green light can result in reduction in pain in variety of pain conditions such as migraine and fibromyalgia. Cutaneous application typically requires exposure on the order of minutes, whereas visual application requires exposure on the order of hours. Both routes of exposure elicit changes centrally in the brainstem and spinal cord, and peripherally in the dorsal root ganglia and nociceptors. The mechanisms of photobiomodulation of pain presented in this review provide a foundation in furtherance of exploration of the utility of phototherapy as a tool in the management of pain.

      Perspective

      This review synopsizes the pathways and mechanisms through which light modulates pain and the therapeutic utility of different colors and exposure modalities of light on pain. Recent advances in photobiomodulation provide a foundation for understanding this novel treatment for pain on which future translational and clinical studies can build upon.

      Key Words

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