Optogenetic activation of spinal microglia triggers chronic pain in mice.
Optogenetic activation of spinal microglia triggers chronic pain in mice.
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DOI：
10.1371/journal.pbio.3001154
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发表时间：
2021-03
期刊：
影响因子：
9.8
通讯作者：
Wu LJ
中科院分区：
文献类型：
--
作者：
Yi MH;Liu YU;Umpierre AD;Chen T;Ying Y;Zheng J;Dheer A;Bosco DB;Dong H;Wu LJ
Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in pain. However, there has not been direct evidence showing that selective microglial activation in vivo is sufficient to induce chronic pain. Here, we used optogenetic approaches in microglia to address this question employing CX3CR1creER/+: R26LSL-ReaChR/+ transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia. We found that activation of ReaChR by red light in spinal microglia evoked reliable inward currents and membrane depolarization. In vivo optogenetic activation of microglial ReaChR in the spinal cord triggered chronic pain hypersensitivity in both male and female mice. In addition, activation of microglial ReaChR up-regulated neuronal c-Fos expression and enhanced C-fiber responses. Mechanistically, ReaChR activation led to a reactive microglial phenotype with increased interleukin (IL)-1β production, which is likely mediated by inflammasome activation and calcium elevation. IL-1 receptor antagonist (IL-1ra) was able to reverse the pain hypersensitivity and neuronal hyperactivity induced by microglial ReaChR activation. Therefore, our work demonstrates that optogenetic activation of spinal microglia is sufficient to trigger chronic pain phenotypes by increasing neuronal activity via IL-1 signaling. This study uses red light activation of channelrhodopsin in spinal microglia to trigger chronic pain hypersensitivity in awake mice, revealing that optogenetic activation of microglia increases IL-1β production via inflammasome activation and calcium elevation, leading to neuronal hyperactivity and chronic pain.
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影响因子：
5.3
作者：
Egan, TM;Khakh, BS
通讯作者：
Khakh, BS
DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
DOI：
10.1126/science.1190721
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gourine AV;Kasymov V;Marina N;Tang F;Figueiredo MF;Lane S;Teschemacher AG;Spyer KM;Deisseroth K;Kasparov S
通讯作者：
Kasparov S
影响因子：
82.9
作者：
Burma, Nicole E.;Bonin, Robert P.;Tuan Trang
通讯作者：
Tuan Trang
影响因子：
5.3
作者：
Hooks, Bryan M.;Lin, John Y.;Svoboda, Karel
通讯作者：
Svoboda, Karel