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Foreword
Anxiety, stress, illness and pain and other problems brought about by social development have gradually become the main reasons that
plague people's modern life.
Scientists are constantly understanding how these problems arise and actively exploring possible scientific solutions
.
Recently, two works jointly completed by Chinese and foreign scientists were published in the journal Science, revealing the neuroscientific mechanism
of reducing anxiety through sleep and pain through sound.
It is hoped that these research results will benefit mankind
in the future.
In this edition of the "Science" Coffee Salon column (4 p.
m.
on October 27, see the end of the article for live registration), we invited the authors of the two papers, Dr.
Yu Xiao and Dr.
Zhou Wenjie, to share their research results
.
At the same time, we also learned about the scientific contribution and significance
of the two works through peer expert review articles published in Science magazine.
Sleep to anxiety, listen to pain
The development of human society to today, on the one hand, science and technology are constantly advancing, promoting the continuous improvement of material life, and on the other hand, with the convenience and frequency of information exchange, people's pace of life is getting faster and faster, and the pressure of competition is gradually increasing
.
The vast majority of professionals experience various degrees of anxiety and psychological stress
for a long time.
The accumulation of these emotions and stress greatly increases the risk to health, so that people have to face various diseases and the resulting pain
in advance.
The emergence of these problems has also prompted scientists to constantly think about how to relieve anxiety, reduce stress and reduce pain
.
Recently, two collaborative efforts by Chinese and foreign scientists have made progress in relieving anxiety and reducing pain, and the results
have been published in the journal Science.
Among them[1], researchers from Imperial College London, Xijing Hospital of China's Fourth Military Medical University and Peking University collaborated to find that mice induced sleep under social stress can enhance rapid eye movement sleep (REM) and accelerate the entry into non-REM sleep.
This type of restorative sleep helped the mice relieve anxiety
caused by social stress.
The authors reveal the neural network mechanisms
behind these phenomena.
Another work [2] researchers from the University of Science and Technology of China, Anhui Medical University and the National Institutes of Health collaborated to reveal the neural mechanisms
of sound analgesia.
Using a range of brain imaging techniques and neural regulation, the authors identified the neural substrates and neural circuits involved in the analgesic effects of sound in mice
.
Science magazine invited peer experts to comment on these two works, and we will comb and understand the main contribution of these two works based on the comments:
sleep anxiety [3].
When mice are placed in a restricted cage with the same kind of habitation, the original occupants may repel and attack the newcomers (peer provocation), causing the newcomers to develop "social defeat stress" (SDS).
。 SDS induces socially frustrated mice to sleep in the next few hours, and researchers such as researcher Yu Xiao from Imperial College London and Professor Dong Hailong's team at Xijing Hospital of the Fourth Military Medical University of China found that this restorative sleep activates a small number of nerve cells located in the ventral tegmental area (VTA) of the midbrain [1].
The role
of specific neural circuits in linking social stress and restorative sleep was revealed.
After identification, the researchers found that most of these VTA cells activated by social stress are γ-aminobutyric acid (GABA)ergic neuronal cells, and only a small number are dopamine neuronal cells
commonly used to regulate reward processing, enhance learning, social achievement and other functions.
These GABAergic neuronal cells were further identified as somatostatin (SST) protein-positive nerve cells rather than microalbumin (PV) positive nerve cells
.
GABA/SST neurons were more active after social defeat and persisted for several hours, maintaining sleep
in a normal physiological state.
The activation of these specific neurons is sufficient necessary to
enhance REM sleep (REM) and non-REM sleep after social defeat.
The authors found that restorative sleep after social frustration reduced already elevated plasma corticosterone concentrations (reducing stress) and reduced anxiety
.
In contrast, sleep deprivation (or suppression of these VTA baroreceptors), plasma corticosterone concentrations remained high, and anxious behavior was not alleviated
.
How exactly is sleep induced after social frustration? The researchers found that GABA-ergy neurons in the VTA region are tightly connected to the brain's baroreceptor network and sleep regulation center
.
Social frustration stress activates the brain's baroreceptor center, which activates GABA/SST neurons in the VTA region of specific stress response and their downstream sleep neural circuits through the link of neural circuits, thereby inducing sleep, and these results reveal an important question
of how restorative sleep occurs after social frustration stress.
Figure 1.
Social frustration activates the regional interconnection of neural circuits in the brain (taken from [3])
Another important question is whether the results of social frustration-induced sleep, recovery of plasma corticosterone concentrations, and reduction of anxiety are causal or occur in parallel? In response to this problem, the authors' experimental results show that sleep produced by VTA GABA/SST baroreceptor neurons can be anxiolytic and reduce corticosterone concentration (stress reduction), but anxiolytic and corticoster concentration are played
by parallel neural circuits.
However, not all mice increase REM sleep
after social stress.
The authors' study showed that about half of the mice increased REM sleep time, while the remaining mice did not change
in sleep duration.
These findings make more general demands on whether the results are more general, with the animals' sex, genetic differences, and growth environment all likely to change sleep patterns and respond to stress
.
Despite these problems, this study provides neural circuit mechanisms for stress stress and sleep that follow, providing a biological basis
for possible treatments in the future.
Listen for the pain [4].
Our perception of physical pain is regulated by environmental factors and other sensory information inputs received, such as sounds
.
The emerging music therapy has also been increasingly used in the relief and treatment of chronic pain, suggesting a relationship between sound and pain perception, and suggesting that pain
may be relieved through sound, such as music.
In fact, as early as 1960, scientists reported in the journal Science that sound can exert a direct and significant pain relief effect
during dental procedures.
Subsequently, a growing body of research has found that different types of music, such as piano music, guitar sounds, and singing voices, can effectively relieve pain, but it is unclear
how sound relieves pain, what key neurons are involved, and the neural mechanisms behind it.
Zhang Zhi's team from the University of Science and Technology of China, Tao Wenjuan's team from Anhui Medical University, and Liu Yuanyuan's team from the National Institutes of Health revealed it in mice through a variety of imaging, tracking techniques and neuromodulationThe neural mechanism
of voice analgesia.
Clearly, studying the relationship between music, sound, and pain through rodents is challenging, starting with ignorance of
whether and how animals can perceive music.
First author Zhou Wenjie and other researchers [2] carried out a series of behavioral tests on pain, and they found that there was no essential difference
in the response of mice to harmonized, uncoordinated or white noise.
It is worth noting that the decisive factor for pain relief is the increase in sound intensity of 5 dB above the ambient sound field, while the increase in sound intensity to 10 dB, 15 dB or 20 dB has little effect
.
When mice are repeatedly exposed to sounds 5 dB above ambient noise, analgesic effects
can last for several days.
Although this new discovery differs from the analgesia evoked in humans using music or pleasure sounds, it still brings a whole new understanding
of sound-induced analgesia.
Neuroimaging studies of the human brain have shown significant changes
in the activity of brain regions associated with pain perception, such as the prefrontal lobe, cingulate cortex, and insular cortex, when listening to music.
A recent study has shown that the insular and prefrontal cortex play a key role in correlating sound signals with the production of pleasant or negative emotions: within 220 milliseconds of a sound, the auditory cortex (ACx) of the brain is rapidly active and projected into other higher cortical regions, such as the insular cortex, suggesting that these areas are involved
in the processing of sound signals.
Unexpectedly, Zhou Wenjie et al.
found a cortical thalamic nerve circuit
that more directly regulates the sound-induced analgesic effect.
Through optogenetics and other research methods, they found that inhibiting the neural projection of the auditory cortex to the somatosensory posterior thalamic nucleus (PO) and ventral posterior nucleus (VP), and then inhibiting the neurons that PO and VP are activated during pain, is the more direct cause
of sound analgesia.
Figure 2 Schematic diagram of how sound affects pain perception (taken from [4])
So what's so special about the difference in sound intensity at 5 dB above ambient noise? This is an extremely interesting and multidisciplinary question
.
Animal instinctively speaking, a small augmented sound relative to environmental noise can evoke instinctive self-defensive behavior
.
It is driven by a centrifugal projection
of the cortex initiated from the auditory cortex.
From an evolutionary perspective, people can understand that sound-driven self-defense behaviors often occur
along with pain suppression.
Along these lines, an interesting direction of research is to deal with how multiple perceptual brain regions work together, such as the upper thalamus, or sensory taste, smell, vision, hearing, and multisensory regions such as the insular cortex
.
Previous reviews of music or sound therapy for pain relief were mainly thought to be distracting
.
Zhou Wenjie et al.
found that the sound-induced analgesic effect itself has a specific neural mechanism
.
The reason is that after removing the added sound, the body will maintain the analgesic effect
that lasts for several days.
Similarly, neither a 5 dB increase in sound nor regulation of the auditory cortex-thalamic pathway changed the indicators associated with anxiety or stress in mice, which provides a possibility for vocal analgesia to be used synergistically with opioid analgesia or anxiety relief, and it is worth further demonstrating this effect
in humans.
However, the regulation of pain by sound is also a double-edged sword
.
Some sounds can trigger or exacerbate pain perception, such as high-intensity sounds that can cause migraines in people with phonophobia
.
The neural circuits revealed by Zhou Wenjie and others to relieve pain may be applied
in humans in the future.
1.
Xiao Yu, et al.
, A specific circuit in the midbrain detexts stress and induces restorative sleep, Science 377, 63 (2022) style="color: rgb(136, 136, 136);font-size: 13px;" _mstmutation="1" _istranslated="1"> 2.
Wenjie Zhou, et al.
, Sound induces analgesia through corticothalamic circuits, Science 377, 198 (2022) style="color: rgb(136, 136, 136);font-size: 13px;" _mstmutation="1" _istranslated="1"> 3.
Marian Joëls, E.
Ronald De Kloet, Sleeping off stress, Science 377, 27 (2022), style="color: rgb(136, 136, 136);font-size: 13px;" _mstmutation="1" _istranslated="1"> 4.
Rohini Kuner and Thomas Kuner, Sounding out pain, Science 377, 155 (2022), style="font-size: 13px;" _mstmutation="1" _istranslated="1">
related live lectures: Sleep reduces anxiety, sound suppresses the neurobiological mechanism
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