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Chronic pain-induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety
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Title: | Chronic pain-induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety |
Authors: | Yamauchi, Naoki Browse this author | Sato, Keiichiro Browse this author | Sato, Kenta Browse this author | Murakawa, Shunsaku Browse this author | Hamasaki, Yumi Browse this author | Nomura, Hiroshi Browse this author →KAKEN DB | Amano, Taiju Browse this author →KAKEN DB | Minami, Masabumi Browse this author →KAKEN DB |
Issue Date: | 27-Apr-2022 |
Publisher: | The American Association for the Advancement of Science(AAAS) |
Journal Title: | Science advances |
Volume: | 8 |
Issue: | 17 |
Start Page: | eabj5586 |
Publisher DOI: | 10.1126/sciadv.abj5586 |
Abstract: | 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. |
Rights: | https://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/86121 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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