Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids
Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids
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不同神经元群通过外源性和内源性阿片类药物介导炎性疼痛镇痛
DOI：
10.7554/elife.55289
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发表时间：
2020-06
期刊：
影响因子：
7.7
通讯作者：
Sun Yan-Gang
中科院分区：
文献类型：
--
作者：
Zhang Xin-Yan;Dou Yan-Nong;Yuan Lei;Li Qing;Zhu Yan-Jing;Wang Meng;Sun Yan-Gang
mu -阿片受体（MORs）在外源性和内源性阿片镇痛中起着至关重要的作用。然而，这两种阿片类镇痛的不同机制在很大程度上仍然未知。在这里，我们证明了外源性和内源性阿片类药物对炎症性疼痛的镇痛作用是由小鼠神经元不同亚群中表达的MORs介导的。我们发现外源性阿片诱导的炎性疼痛镇痛是由Vglut2+谷氨酸能神经元而非gaba能神经元的MORs介导的。相比之下，内源性阿片镇痛是由gaba能神经元的MORs介导的，而不是Vglut2+谷氨酸能神经元。此外，脊髓水平表达的MORs主要参与吗啡对急性疼痛的镇痛作用，而不参与慢性炎性疼痛的内源性阿片类镇痛作用。因此，我们的研究揭示了外源性和内源性阿片镇痛的不同机制，为进一步剖析阿片镇痛的回路机制奠定了基础。
Mu-opioid receptors (MORs) are crucial for analgesia by both exogenous and endogenous opioids. However, the distinct mechanisms underlying these two types of opioid analgesia remain largely unknown. Here, we demonstrate that analgesic effects of exogenous and endogenous opioids on inflammatory pain are mediated by MORs expressed in distinct subpopulations of neurons in mice. We found that the exogenous opioid-induced analgesia of inflammatory pain is mediated by MORs in Vglut2+ glutamatergic but not GABAergic neurons. In contrast, analgesia by endogenous opioids is mediated by MORs in GABAergic rather than Vglut2+ glutamatergic neurons. Furthermore, MORs expressed at the spinal level is mainly involved in the analgesic effect of morphine in acute pain, but not in endogenous opioid analgesia during chronic inflammatory pain. Thus, our study revealed distinct mechanisms underlying analgesia by exogenous and endogenous opioids, and laid the foundation for further dissecting the circuit mechanism underlying opioid analgesia.
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影响因子：
64.8
作者：
Skarnes WC;Rosen B;West AP;Koutsourakis M;Bushell W;Iyer V;Mujica AO;Thomas M;Harrow J;Cox T;Jackson D;Severin J;Biggs P;Fu J;Nefedov M;de Jong PJ;Stewart AF;Bradley A
通讯作者：
Bradley A
影响因子：
3.7
作者：
Weibel R;Reiss D;Karchewski L;Gardon O;Matifas A;Filliol D;Becker JA;Wood JN;Kieffer BL;Gaveriaux-Ruff C
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Gaveriaux-Ruff C
影响因子：
13.9
作者：
Corder G;Castro DC;Bruchas MR;Scherrer G
通讯作者：
Scherrer G
影响因子：
25
作者：
Rodriguez E;Sakurai K;Xu J;Chen Y;Toda K;Zhao S;Han BX;Ryu D;Yin H;Liedtke W;Wang F
通讯作者：
Wang F
影响因子：
15.9
作者：
Lutz PE;Kieffer BL
通讯作者：
Kieffer BL