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

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 add 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.

Systems and Circuits Linking Chronic Pain and Circadian Rhythms

“…A different study in rats showed that red light exposure for either 8 or 3 h a day led to hyperalgesia without the need for any physical injury or intentional inflammation (Khanna et al, 2019). This group reported that red light induced increasing hyperalgesia with either increased luminance or consecutive days of prolonged red-light exposure and that could be returned to baseline by reverting back to normal room light.…”

“…As mentioned above, bright light therapy has also shown some efficacy in treating patients with chronic pain. Both blue and green light have been shown to decrease paw withdrawal latency, a measure of hyperalgesia in WT rats (Khanna et al, 2019). Green light has been most heavily investigated for clinical use.…”

Constant Light Exerted Detrimental Cardiovascular Effects Through Sympathetic Hyperactivity in Normal and Heart Failure Rats

“…High intensity of light is a treatment for post-traumatic brain injury patients who are lack of sunlight exposure (Dams-O'Connor et al, 2019). Exposure to red light could result in a time-and dose-dependent thermal hyperalgesia and mechanical allodynia (Khanna et al, 2019). The green light was reported to aggravate high-fat diet-induced obesity and metabolic disorders in male mice (Zhang et al, 2019).…”

Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial

“…We recently reported that exposure to lights of different wavelengths can affect nociception in rodents (18,19). For example, exposure to a green light emitting diode (GLED) resulted in antinociception in naïve rats and antihyperalgesia in rats with neuropathic pain that was dependent on engagement of the visual system.…”