The anterior cingulate cortex projection to the dorsomedial striatum modulates hyperalgesia in a chronic constriction injury mouse model.

The anterior cingulate cortex projection to the dorsomedial striatum modulates hyperalgesia in a chronic constriction injury mouse model.
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前扣带皮层投射到背内侧纹状体调节慢性压迫性损伤小鼠模型的痛觉过敏

DOI:
10.5114/aoms.2019.85202
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发表时间:
2021
期刊:
Archives of medical science : AMS
影响因子:
--
通讯作者:
Wang J
Wang J
中科院分区:
其他
文献类型:
--
作者:
Zhuang X;Huang L;Gu Y;Wang L;Zhang R;Zhang M;Li F;Shi Y;Mo Y;Dai Q;Wei C;Wang J

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本研究旨在研究前扣带皮层(ACC)-背侧中脑纹状体(DMS)在神经病理性疼痛中的作用。光遗传学越来越多地用于神经科学研究,以选择性地精确控制一组确定的中枢神经元的活动,以确定它们在动物行为功能中的作用。最重要的视蛋白是蓝色敏感的ChR 2和黄色敏感的NpHR。钙-钙调蛋白依赖性蛋白激酶Ⅱ α(CaMKIIα)主要表达于锥体兴奋性神经元。在小鼠的ACC区注射AAV 2/9-CamKII-ChR 2-mCherry、AAV 2/9-CamKII-eNpHR 3.0-GFP或AAV 2/9-CamKII-mCherry病毒,并在ACC或DMS区进行光纤植入。然后跟踪小鼠2至8周,并在存在或不存在蓝/黄光(473 nm/589 nm)的情况下进行行为测试。建立大鼠坐骨神经慢性压迫性损伤模型(CCI)后第3天和第7天,分别进行有无蓝/黄光刺激的痛行为学测试。测定各组小鼠左、右后肢痛阈。无论是激活ACC还是DMS神经元,与正常小鼠相比,ChR 2-off-right组和mCherry-on-right组的热痛阈和机械痛阈均显著降低。当抑制ACC或DMS神经元时,CCI术后第3天和第7天,NpHR-on-right组CCI小鼠的热痛阈值和机械痛阈值显著高于NpHR-off-right组和mCherry-on-right组。前扣带皮层-背侧中脑纹状体可能参与神经病理性疼痛的调节。
The aim of the study was to study the role of the anterior cingulate cortex (ACC)-dorsal midbrain striatum (DMS) in neuropathic pain in mice. Optogenetics has been increasingly used in neuroscience research to selectively and precisely control the activity of a defined group of central neurons to determine their roles in behavioral functions in animals. The most important opsins are blue-sensitive ChR2 and yellow-sensitive NpHR. Calcium-calmodulin dependent protein kinase Iiα (CaMKIIα) is mostly expressed in the pyramidal excitatory neurons. Mice were injected with AAV2/9-CamKII-ChR2-mCherry, AAV2/9-CamKII-eNpHR3.0-GFP or AAV2/9-CamKII-mCherry virus in the ACC region, and the optical fiber implantation was performed in the ACC or DMS region. Mice were then followed up for 2 to 8 weeks and behavioral tests were carried out in the presence or absence of the blue/yellow light (473 nm/589 nm). Pain behavioral tests with or without the blue/yellow light at the same time were performed on the third and the seventh day after the chronic constriction injury of sciatic nerve model (CCI) was established. The pain thresholds of left and right hind limbs of mice in all groups were measured. No matter whether activating the neurons in ACC or DMS, compared with normal mice in the ChR2-off-right group, and the mCherry-on-right group, the thermal pain threshold and mechanical pain threshold of the normal mice in the ChR2-on-right group were significantly lower. When inhibiting the neurons in the ACC or DMS, on day 3 and day 7 after CCI operation, the thermal pain threshold and mechanical pain threshold of the CCI mice of the NpHR-on-right group were significantly higher compared with the NpHR-off-right and mCherry-on-right groups. The anterior cingulate cortex-dorsal midbrain striatum may be involved in the regulation of neuropathic pain in mice.
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