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J Pain. 2019 May 2. pii: S1526-5900(18)30814-9. doi: 10.1016/j.jpain.2019.04.008. [Epub ahead of print]

Development and Characterization of An Injury-free Model of Functional Pain in Rats by Exposure to Red Light.

Author information

1
Departments of Anesthesiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; Departments of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; Departments of Graduate Interdisciplinary Program in Neuroscience; College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
2
Departments of Anesthesiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; Departments of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
3
Departments of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
4
Departments of Anesthesiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
5
Departments of Anesthesiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; Departments of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. Electronic address: mibrahim@anesth.arizona.edu.

Abstract

We report the development and characterization of a novel, injury-free rat model in which nociceptive sensitization following red light is observed in multiple body areas reminiscent of widespread pain in functional pain syndromes. Rats were exposed to red light emitting diodes (RLED) (LEDs, 660 nanometer) at an intensity of 50 Lux for 8 hours daily for 5 days resulting in time- and dose-dependent thermal hyperalgesia and mechanical allodynia in both male and female rats. Females showed earlier onset of mechanical allodynia than males. The pronociceptive effects of RLED were mediated through the visual system. RLED-induced thermal hyperalgesia and mechanical allodynia were reversed with medications commonly used for widespread pain including gabapentin, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, and NSAIDs. Acetaminophen failed to reverse the RLED induced hypersensitivity. The hyperalgesic effects of RLED were blocked when bicuculline, a GABA-A receptor antagonist, was administered into the rostral ventromedial medulla (RVM) suggesting a role for increased descending facilitation in the pain pathway. Key experiments were subjected to a replication study with randomization, investigator-blinding, inclusion of all data and high levels of statistical rigor. RLED induced thermal hyperalgesia and mechanical allodynia without injury offers a novel injury free rodent model useful for the study of functional pain syndromes with widespread pain. RLED exposure also emphasizes the different biological effects of different colors light exposure. Perspective: This study demonstrates the effect of light exposure on nociceptive thresholds. These biological effects of red LED adds evidence to the emerging understanding of biological effects of light of different colors in animals and humans. Understanding the underlying biology of red light-induced wide spread pain may offer insights into functional pain states.

KEYWORDS:

Diffuse hypersensitivity; Functional pain Syndromes; Injury-free; Red Light Emitting Diode; Wide spread pain

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