Chronic pain-induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety.
Chronic pain-induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety.
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DOI：
10.1126/sciadv.abj5586
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发表时间：
2022-04-29
期刊：
影响因子：
13.6
通讯作者：
Minami, Masabumi
中科院分区：
文献类型：
--
作者：
Yamauchi, Naoki;Sato, Keiichiro;Sato, Kenta;Murakawa, Shunsaku;Hamasaki, Yumi;Nomura, Hiroshi;Amano, Taiju;Minami, Masabumi
慢性疼痛和精神功能障碍（如抑郁症和焦虑症）的合并症早已被认识，但其潜在机制仍知之甚少。在这里，使用神经性疼痛的小鼠模型，我们证明了终纹床核（BNST）的神经元可塑性，这在慢性疼痛引起的适应不良焦虑中起着关键作用。电生理学表明，慢性疼痛增加抑制输入外侧下丘脑（LH）投射BNST神经元。化学遗传操作显示，LH投射BNST神经元的持续抑制在慢性疼痛诱导的焦虑中起着至关重要的作用。此外，我们还利用分子遗传学方法证明，慢性疼痛可提高BNST神经元一个特定亚群的兴奋性，该亚群表达可卡因和苯丙胺调节转录物（CART）。CART阳性神经元的兴奋性升高导致LH投射BNST神经元的抑制性输入增加，从而诱导焦虑样行为。这些发现揭示了慢性疼痛如何诱发以适应不良焦虑为特征的精神障碍。在神经病理性疼痛的小鼠模型中，边缘回路中的神经元可塑性导致适应不良的焦虑。
The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain–induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)–projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain–induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety. Neuronal plasticity in the limbic circuit causes maladaptive anxiety in a mouse model of neuropathic pain.
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影响因子：
25
作者：
Li, Haohong;Penzo, Mario A.;Taniguchi, Hiroki;Kopec, Charles D.;Huang, Z. Josh;Li, Bo
通讯作者：
Li, Bo
在大鼠和人类中持续的恐惧：恐惧与焦虑中的杏仁核的作用。
DOI：
10.1038/npp.2009.109
发表时间：
2010-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
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影响因子：
64.8
作者：
Ciocchi, Stephane;Herry, Cyril;Luethi, Andreas
通讯作者：
Luethi, Andreas
影响因子：
25
作者：
Giardino WJ;Eban-Rothschild A;Christoffel DJ;Li SB;Malenka RC;de Lecea L
通讯作者：
de Lecea L
影响因子：
64.8
作者：
Marcinkiewcz, Catherine A.;Mazzone, Christopher M.;D'Agostino, Giuseppe;Halladay, Lindsay R.;Hardaway, J. Andrew;DiBerto, Jeffrey F.;Navarro, Montserrat;Burnham, Nathan;Cristiano, Claudia;Dorrier, Cayce E.;Tipton, Gregory J.;Ramakrishnan, Charu;Kozicz, Tamas;Deisseroth, Karl;Thiele, Todd E.;McElligott, Zoe A.;Holmes, Andrew;Heisler, Lora K.;Kash, Thomas L.
通讯作者：
Kash, Thomas L.