Neuron: Following antidepressant and memory enhancement, Ren Chaoran's team revealed the neural circuit of light therapy to relieve pain

Exposure to bright light in the morning can improve sleep and mood
.

Compared with drug treatment, this morning light treatment has fewer side effects: experiments have shown that continuous morning light treatment in autumn and winter does not cause eye lesions for 6 years

Morning exposure to bright light may improve sleep and mood

The rodent ventrolateral geniculate body and intergenic lobule (vLGN/IGL) serve as a relay station for the visual system, receiving visual stimuli from the retina and transmitting them to the visual cortex
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On March 8, 2022, the research team of Ren Chaoran from Jinan University revealed in the journal Neuron the visual neural circuit mechanism of long-term phototherapy for pain relief
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Figure 1: Virus tracing experiments to resolve the vLGN/IGL→l/vlPAG loop

Figure 1: Analysis of the vLGN/IGL→l/vlPAG loop from the virus tracer experiment Figure 1: The vLGN/IGL→l/vlPAG loop of the virus tracer experiment

The researchers injected cre enzyme retrograde tracer virus rAAV-Retro-Cre into lateral and ventrolateral periaqueductal gray matter (l/vlPAG), and injected cre enzyme-dependent expression of AAV-DIO-eYFP in vLGN/IGL (Figure 1).
, and showed by immunofluorescence experiments that the vast majority of vLGN/IGL inhibitory neurons (92.
48% of green fluorescently labeled neurons in this region express GABA) project to l/vlPAG
.

Through a similar experimental strategy, it was found that fibers receiving vLGN/IGL projections mainly form connections with inhibitory neurons in the l/vlPAG area, suggesting that anatomically, vLGN/IGL inhibitory neurons can directly innervate inhibitory neurons in the l/vlPAG area.
Yuan
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After activating the vLGN/IGL→l/vlPAG circuit by light, the isolated brain slices found that neurons in the l/vlPAG brain region mainly exhibit inhibitory postsynaptic current effects, which can be antagonized by GABA-A receptors agent blocking
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This further suggests functionally that vLGN/IGL inhibitory neurons directly inhibit inhibitory neurons in the l/vlPAG area through projections

Figure 2: Fiber optic calcium imaging records neuronal signals activated by pain stimuli

Figure 2: Fiber optic calcium imaging records neuronal signals activated by pain stimuli Figure 2: Fiber optic calcium imaging records pain stimuli-activated neuronal signals

Previous studies have shown that inhibitory neurons in the l/vlPAG brain region encode pain-related signals
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By injecting calcium ion indicator in the l/vlPAG brain region, they found that pain-related noxious stimuli (plantar shock, hot plate test, etc.

Chronic activation of the vLGN/IGL→l/vlPAG circuit can increase the threshold of normal mice to nociceptive stimuli and relieve pain symptoms in inflammatory pain model animals
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These experimental results suggest that the vLGN/IGL→l/vlPAG loop encodes pain-related information

Figure 3: Retrograde tracer virus resolves the RGC→vLGN/IGL→l/vlPAG loop

Figure 3: Retrograde tracer virus resolves RGC→vLGN/IGL→l/vlPAG loop Figure 3: Retrograde tracer virus resolves RGC→vLGN/IGL→l/vlPAG loop

Further, it was found that retinal ganglion cells (RGCs) can receive retrograde projections from the vLGN/IGL→l/vlPAG loop based on the modified tracer rabies virus, indicating that the vLGN/IGL→l/vlPAG loop can directly accept the retrograde projections from the vLGN/IGL→l/vlPAG loop.
The input of the RGC (hereafter referred to as the RGC→vLGN/IGL→l/vlPAG loop, Fig.
3)
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Chronic activation of this loop exerts an antinociceptive effect similar to activation of the vLGN/IGL→l/vlPAG loop

Based on the above experimental results, the researchers speculated whether external light stimuli would play a similar anti-nociceptive effect.
By setting different gradients of light (200, 1000, 3000 or 5000 lux, it was found that light above 3000 lux intensity can cause normal mice.
Anti-harm behavior
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By fiber optic calcium imaging, it was found that exposure of mice to light at an intensity of 3000 lux inhibited neuronal activity in the l/vlPAG brain region
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In addition, the neuronal activity in the l/vlPAG brain region was increased after the pain stimulation, and the neuronal activity decreased rapidly after the above-mentioned strong light stimulation

Formalin injection in the forepaw of mice elicited a pain response (licking the forepaw), and a single 3000 lux optical fiber exposure was able to reduce the licking time of the mice
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Figure 4: Long-term phototherapy exerts an antinociceptive effect

Figure 4: Long-term phototherapy exerts anti-nociceptive effects Figure 4: Long-term phototherapy exerts anti-nociceptive effects

Complete Freund's adjuvant (CFA)-induced inflammatory pain model mice can significantly prolong the latency of paw withdrawal in the hot plate test and improve the pain threshold after exposure to light with an intensity of 3000 lux for 2 hours a day for one week.
This damage-resistant behavior effect increases with the duration of light exposure
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In another pain model (CCI), more than 2 weeks of light exposure at 3000 lux intensity was required to exert an antinociceptive effect

In contrast, chronic inhibition of the RGC→vLGN/IGL→l/vlPAG loop in the CCI pain model and the formalin pain model did not induce antinociceptive effects after exposure to light at an intensity of 3000 lux
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These results suggest that strong light exposure exerts antinociceptive effects dependent on the activation of the RGC→vLGN/IGL→l/vlPAG loop

Collectively, this paper reveals the neural circuit mechanism by which phototherapy relieves pain symptoms by activating the RGC→vLGN/IGL→l/vlPAG circuit
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light therapy light therapy pain relief relief pain relief

Original source:

Original source:

Zhengfang Hu, et al.
A visual circuit related to the periaqueductal gray area for the anticiceptive effects of bright light treatment .
Neuron, 2022.

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