Long-term upregulation of cortical glutamatergic AMPA receptors in a mouse model of chronic visceral pain.
Long-term upregulation of cortical glutamatergic AMPA receptors in a mouse model of chronic visceral pain.
复制标题
慢性内脏痛小鼠模型中皮质谷氨酸能 AMPA 受体的长期上调
DOI：
10.1186/s13041-015-0169-z
复制
发表时间：
2015-11-19
期刊：
影响因子：
3.6
通讯作者：
Zhuo M
中科院分区：
文献类型：
--
作者：
Liu SB;Zhang MM;Cheng LF;Shi J;Lu JS;Zhuo M
肠易激综合征（Irritable bowel syndrome，IBS）是一种常见的功能性胃肠病，可引起持续的内脏疼痛和不适。AMPA受体介导的长时程增强（LTP）已被证明在神经性疼痛和炎性疼痛的动物模型中起关键作用。没有报告是可用于慢性内脏pain.ResultsIn这项研究中，我们使用综合的方法来探讨潜在的中央前扣带皮层（ACC）的内脏痛小鼠模型诱导的结肠内注射酵母多糖的变化在ACC的中央变化。我们发现内脏痛通过增强AMPA受体向膜的运输诱导ACC中AMPA受体（在突触后）的表达增加。GluA 1和GluA 2/3亚基均显著增加。支持生化变化，兴奋性突触传递在ACC也显着增强。ACC内微量注射AMPA受体抑制剂IEM 1460可抑制内脏痛和自发痛行为。此外，我们发现，GluA 1在Ser 845位点的磷酸化增加，这表明GluA 1磷酸化可能有助于AMPA受体的运输。使用基因敲除小鼠缺乏钙-钙调素刺激腺苷酸环化酶亚型1（AC 1），我们发现，AMPA受体磷酸化和其膜贩运诱导酵母聚糖injection.ConclusionsOur结果提供了直接的证据皮质AMPA受体，以促进酵母聚糖诱导的内脏和自发性疼痛和抑制AC 1活性可能有助于减少慢性内脏痛。
BackgroundIrritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and it causes long-lasting visceral pain and discomfort. AMPA receptor mediated long-term potentiation (LTP) has been shown to play a critical role in animal models of neuropathic and inflammatory pain. No report is available for central changes in the ACC of mice with chronic visceral pain.ResultsIn this study, we used integrative methods to investigate potential central plastic changes in the anterior cingulate cortex (ACC) of a visceral pain mouse model induced by intracolonic injection of zymosan. We found that visceral pain induced an increased expression of AMPA receptors (at the post synapses) in the ACC via an enhanced trafficking of the AMPA receptors to the membrane. Both GluA1 and GluA2/3 subunits were significantly increased. Supporting biochemical changes, excitatory synaptic transmission in the ACC were also significantly enhanced. Microinjection of AMPA receptor inhibitor IEM1460 into the ACC inhibited visceral and spontaneous pain behaviors. Furthermore, we found that the phosphorylation of GluA1 at the Ser845 site was increased, suggesting that GluA1 phosphorylation may contribute to AMPA receptor trafficking. Using genetically knockout mice lacking calcium-calmodulin stimulated adenylyl cyclase subtype 1 (AC1), we found that AMPA receptor phosphorylation and its membrane trafficking induced by zymosan injection were completely blocked.ConclusionsOur results provide direct evidence for cortical AMPA receptors to contribute to zymosan-induced visceral and spontaneous pain and inhibition of AC1 activity may help to reduce chronic visceral pain.
影响因子：
2
作者：
Zhu X;Zhu X;Chen W;Chen J
通讯作者：
Chen J