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

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.

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

“…Music has been shown to produce analgesia in humans (25-27, 80, 82, 134) and in rats (43). Recent studies also suggest analgesic activities of exposure to light in both humans and rats (135,136). The antinociceptive effects of the green LED light were associated with down-regulation of N-type calcium channels in dorsal root ganglion neurons, as well as were reversed by naloxone, thus also implicating the opioid-based analgesic mechanism (136).…”

“…Recent studies also suggest analgesic activities of exposure to light in both humans and rats (135,136). The antinociceptive effects of the green LED light were associated with down-regulation of N-type calcium channels in dorsal root ganglion neurons, as well as were reversed by naloxone, thus also implicating the opioid-based analgesic mechanism (136). Herein, we propose that studying combinations of multiple non-pharmacological modalities can lead to non-invasive and non-addictive treatments of pain ("digital analgesics") which can also result in lowering effective doses of analgesics and improving pain relief.…”

Enriched Environment and Effects on Neuropathic Pain: Experimental Findings and Mechanisms

“…Consequently, EE may help to reduce opioid consumption in pain management. Moreover, a pronounced decrease of the N‐type calcium channel, which governs excitatory neurotransmission, was detected in rats exposed to green LED light after nerve injury . The research infers that the reduction of calcium influx may also account for the antiallodynic and antihyperalgesic effects.…”

“…Currently, 2 out of the 3 EE studies without a running wheel have shown a significant reduction in pain response following peripheral nerve injury (see Table ). One study has explored phototherapy for pain relief, which can be considered as a sole visual enrichment . Intriguingly, exposure to green LED light not only increased acute sensory thresholds to noxious thermal stimulus in naïve rats, but also reversed mechanical allodynia and thermal hyperalgesia in spinal nerve ligated rats.…”

New therapies to relieve pain

“…Migraine in particular often does not respond to traditional drugs including opioids. A recent study has shown some efficacy for a surprising therapy against migraine based on green light . The researchers bathed rats under LED light at various wavelengths in the visible spectrum for 8 h a day and compared their tolerance to neuropathic pain.…”