Abstract
Visual exposure to dim, green, light has been found to reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green light was due to the central release of endogenous opioids and a reduction in inflammatory cytokines in the cerebrospinal fluid. The present study assessed the effect of green light therapy (GLT) on joint pain in a rat model of osteoarthritis (OA) and investigated the role of endolipids. Male and female Wistar rats (207-318 g) received an intra-articular injection of sodium monoiodoacetate (3 mg in 50 μL saline) into the knee to induce OA. On day 9, animals were placed in a room illuminated by either white (neutral-white 4000K; 20 lux) or green (wavelength: 525 nm; luminance: 20 lux) light for 5 days (8 hours per day). Joint nociception was assessed by von Frey hair algesiometry, dynamic weight bearing, and in vivo single unit extracellular recordings from knee joint mechanonociceptors. Compared to white light, GLT significantly reduced secondary mechanical hypersensitivity in both sexes and improved hindlimb weight bearing in females only. There was no effect of GLT on joint nociceptor activity in either sex. Serum lipidomics indicated an increase in circulating analgesic endolipids in response to GLT, particularly the N -acyl-glycines. Partial blockade of the endocannabinoid system with the G protein receptor-18/cannabinoid-1 receptor antagonist AM281 (500 μg/kg i.p.) attenuated GLT-induced analgesia. These data show for the first time that GLT acts to reduce OA pain by upregulating circulating analgesic endolipids, which then engage the endocannabinoid system.