The study revealed the neural mechanisms of opioid analgesics.

On June 10, eLife published an online research paper entitled "analgesic effect of exogenous and endogenous opioids on different neuronal populations mediating inflammatory pain". The research was conducted by sun Yangang, Center for excellence and innovation in brain science and intelligent technology, Chinese Academy of Sciences, Shanghai brain science and brain like research center, and state Key Laboratory of neuroscience The research group completed.this study, combined with genetic manipulation, pharmacological experiments, fiber-optic calcium recording and behavioral experiments, revealed that exogenous and endogenous opioids exert analgesic effects on mu opioid receptors (MOR) expressed in glutamatergic and GABA ergic neurons respectively in inflammatory pain.this study provides a new way to analyze the function of opioid system and further study the pain regulation loop.pain is a complex feeling. As a protective mechanism, normal pain feeling is very important for the survival of animals and people. However, the quality of life of patients is seriously affected by the severe injury of the body or chronic pain caused by chronic diseases.persistent or recurrent pain is one of the current clinical treatment problems, which affects more than 20% of the global population.therefore, it is necessary to find a suitable, powerful and effective analgesic method.among the numerous pain treatment methods, opioids have been used for analgesia as early as a thousand years ago, and have become the most effective analgesic drugs in clinic. However, the long-term use of opioids is limited by many serious side effects.at present, the neural mechanism of opioid analgesia is not completely clear. Therefore, it is necessary to study the analgesic mechanism of opioids for the development of new drugs with less side effects.exogenous and endogenous opioids exert analgesic effects by acting on the mu opioid receptor (MOR), which is widely expressed in the nervous system.in order to analyze the mechanism of action of exogenous and endogenous opioids, the researchers used an experimental strategy of "knock out first, then restore the expression of MOR in situ", and specifically studied the function of MOR in the analgesic effect of opioids in different types of neurons.studies have found that exogenous opioids (such as morphine) produce analgesic effect by acting on mor in glutamatergic excitatory neurons, while endogenous opioids released from the organism can alleviate chronic inflammatory pain by acting on the mor in inhibitory neurons.the researchers further elucidated the role of MOR in analgesia at peripheral, spinal and supraspinal levels.at the spinal cord level, MOR expressed in the spinal dorsal horn neurons mainly mediates the analgesic effect of morphine in acute pain, but does not participate in endogenous opioid analgesia.in addition, MOR in excitatory neurons and inhibitory neurons of spinal cord have opposite functions in pain regulation. The activation of MOR in excitatory neurons of spinal cord causes analgesic effect, while mor in inhibitory neurons of spinal cord causes hyperalgesia.the researchers also found that at the spinal level, MOR expressed in the parabrachial nucleus was involved in the analgesic effect of morphine in inflammatory pain.this study shows that endogenous and exogenous opioids exert analgesic effects through different targets.in combination with the research group's research published online in neuroscience bulletin in May 2020, this study reveals the role of MOR in different types of neurons in opioid analgesia and opioid dependence, which provides an important basis for further elucidating the mechanism of opioid action and improving the application of opioid drugs. under the guidance of researcher sun Yangang, this study was mainly completed by Zhang Xinyan and Dou Yannong, doctoral students of brain intelligence Excellence Center. Yuan Lei, Li Qing, Zhu Yanjing and Wang Meng of the research group also made important contributions. the project is supported by the National Natural Science Foundation of China, Shanghai Municipality and the Chinese Academy of Sciences. model map of opioid analgesia mechanism