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Long-lasting antinociceptive effects of green light in acute and chronic pain in rats

Ibrahim, Mohab M.; Patwardhan, Amol; Gilbraith, Kerry B.; Moutal, Aubin; Yang, Xiaofang; Chew, Lindsey A.; Largent-Milnes, Tally; Malan, T. Philip; Vanderah, Todd W.; Porreca, Frank; Khanna, Rajesh

doi: 10.1097/j.pain.0000000000000767
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Abstract: Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain. Rats receiving green LED light (wavelength 525 nm, 8 h/d) showed significantly increased paw withdrawal latency to a noxious thermal stimulus; this antinociceptive effect persisted for 4 days after termination of last exposure without development of tolerance. No apparent side effects were noted and motor performance was not impaired. Despite LED exposure, opaque contact lenses prevented antinociception. Rats fitted with green contact lenses exposed to room light exhibited antinociception arguing for a role of the visual system. Antinociception was not due to stress/anxiety but likely due to increased enkephalins expression in the spinal cord. Naloxone reversed the antinociception, suggesting involvement of central opioid circuits. Rostral ventromedial medulla inactivation prevented expression of light-induced antinociception suggesting engagement of descending inhibition. Green LED exposure also reversed thermal and mechanical hyperalgesia in rats with spinal nerve ligation. Pharmacological and proteomic profiling of dorsal root ganglion neurons from green LED-exposed rats identified changes in calcium channel activity, including a decrease in the N-type (CaV2.2) channel, a primary analgesic target. Thus, green LED therapy may represent a novel, nonpharmacological approach for managing pain.

Repeated exposure to 525 nm wavelength green light is antinociceptive in naive rats and antihyperalgesic in rats with experimental neuropathic pain.

Departments of aAnesthesiology and

bPharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA

Corresponding author. Address: Department of Anesthesiology, College of Medicine, University of Arizona, 1501 North Campbell Dr, PO Box 245050, Tucson, AZ 85724, USA. Tel.: (520) 626-4281; fax: (520) 626-2204. E-mail address: mibrahim@anesth.arizona.edu (M. M. Ibrahim).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received May 27, 2016

Received in revised form October 24, 2016

Accepted October 26, 2016

© 2017 International Association for the Study of Pain
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