Chronic inflammatory pain decreases the glutamate vesicles in presynaptic terminals of the nucleus accumbens.
Chronic inflammatory pain decreases the glutamate vesicles in presynaptic terminals of the nucleus accumbens.
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慢性炎性疼痛会减少伏隔核突触前末梢的谷氨酸小泡
DOI：
10.1177/1744806918781259
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Qi C;Guo B;Ren K;Yao H;Wang M;Sun T;Cai G;Liu H;Li R;Luo C;Wang W;Wu S
奖赏系统在伤害性行为中起着重要作用，而丘脑核（NAc）是奖赏回路中的一个关键节点。多巴胺系统通过调节NAc来影响痛觉，但NAc内的多巴胺能投射在慢性痛的调节中的作用尚不清楚。在本研究中，我们使用完全弗氏佐剂诱导的慢性炎症疼痛模型来探讨NAc中的谷氨酸能终末的变化，我们发现，在慢性炎症后，NAc中的囊泡谷氨酸转运体1（VGLUT 1）的蛋白水平显著降低。免疫荧光染色进一步显示慢性炎症痛后NAc多巴胺受体2（D2 R）棘状投射神经元中VGLUT 1阳性终末的表达减少。此外，使用全细胞记录在双转基因小鼠，其中多巴胺受体1和D2 R表达的神经元可以可视化，我们发现，自发兴奋性突触后电流的频率显着降低，诱发兴奋性突触后电流的成对脉冲比增加D2 R神经元，但不完全弗氏佐剂组的NAc多巴胺受体1神经元。此外，可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体复合物的异常表达有助于减少谷氨酸囊泡的形成。因此，我们的研究结果表明，减少谷氨酸释放的间接途径的NAc可能是一个重要的机制，慢性疼痛的突触前机制在慢性疼痛调节提供了一个新的证据。
Reward system has been proved to be important to nociceptive behavior, and the nucleus accumbens (NAc) is a key node in reward circuitry. It has been further revealed that dopamine system modulates the NAc to influence the pain sensation, whereas the role of glutamatergic projection in the NAc in the modulation of chronic pain is still elusive. In this study, we used a complete Freund’s adjuvant-induced chronic inflammatory pain model to explore the changes of the glutamatergic terminals in the NAc, and we found that following the chronic inflammation, the protein level of vesicular glutamate transporter1 (VGLUT1) was significantly decreased in the NAc. Immunofluorescence staining further showed a reduced expression of VGLUT1-positive terminals in the dopamine receptor 2 (D2R) spiny projection neurons of NAc after chronic inflammatory pain. Furthermore, using a whole-cell recording in double transgenic mice, in which dopamine receptor 1- and D2R-expressing neurons can be visualized, we found that the frequency of spontaneous excitatory postsynaptic currents was significantly decreased and paired-pulse ratio of evoked excitatory postsynaptic currents was increased in D2R neurons, but not in dopamine receptor 1 neurons in NAc of complete Freund’s adjuvant group. Moreover, the abnormal expression of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex contributed to the reduced formation of glutamate vesicles. Hence, our results demonstrated that decreased glutamate release in the indirect pathway of the NAc may be a critical mechanism for chronic pain and provided a novel evidence for the presynaptic mechanisms in chronic pain regulation.
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影响因子：
16.2
作者：
Baliki, Marwan N.;Geha, Paul Y.;Fields, Howard L.;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania
影响因子：
3.3
作者：
Greaves, Jennifer;Prescott, Gerald R.;Chamberlain, Luke H.
通讯作者：
Chamberlain, Luke H.
影响因子：
16.2
作者：
Bromberg-Martin, Ethan S.;Matsumoto, Masayuki;Hikosaka, Okihide
通讯作者：
Hikosaka, Okihide
影响因子：
3.3
作者：
Ford CP
通讯作者：
Ford CP
慢性炎症疼痛损害 mGluR5 介导的去极化诱导的前扣带皮层兴奋抑制
影响因子：
3.7
作者：
Guo, Baolin;Wang, Jiaqi;Wu, Shengxi
通讯作者：
Wu, Shengxi