Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture

Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emot...

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Main Authors: Yiping Xie, Zui Shen, Xixiao Zhu, Yushuang Pan, Haiju Sun, Mengdi Xie, Qiuzhu Gong, Qunqi Hu, Jie Chen, Zemin Wu, Shuting Zhou, Boyu Liu, Xiaofen He, Boyi Liu, Xiaomei Shao, Jianqiao Fang
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923024002260
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author Yiping Xie
Zui Shen
Xixiao Zhu
Yushuang Pan
Haiju Sun
Mengdi Xie
Qiuzhu Gong
Qunqi Hu
Jie Chen
Zemin Wu
Shuting Zhou
Boyu Liu
Xiaofen He
Boyi Liu
Xiaomei Shao
Jianqiao Fang
author_facet Yiping Xie
Zui Shen
Xixiao Zhu
Yushuang Pan
Haiju Sun
Mengdi Xie
Qiuzhu Gong
Qunqi Hu
Jie Chen
Zemin Wu
Shuting Zhou
Boyu Liu
Xiaofen He
Boyi Liu
Xiaomei Shao
Jianqiao Fang
author_sort Yiping Xie
collection DOAJ
description Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain.
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spelling doaj-art-90d6f024487b4d3683a00778816affb32025-08-20T02:13:20ZengElsevierBrain Research Bulletin1873-27472024-11-0121811109210.1016/j.brainresbull.2024.111092Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupunctureYiping Xie0Zui Shen1Xixiao Zhu2Yushuang Pan3Haiju Sun4Mengdi Xie5Qiuzhu Gong6Qunqi Hu7Jie Chen8Zemin Wu9Shuting Zhou10Boyu Liu11Xiaofen He12Boyi Liu13Xiaomei Shao14Jianqiao Fang15Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Acupuncture and Moxibustion, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China; Correspondence to: Department of Tuina, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China; Correspondence to: Department of Tuina, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.Chronic pain, such as neuropathic pain, can lead to anxiety, depression, and other negative emotions, thereby forming comorbidities and increasing the risk of chronic pain over time. Both the infralimbic amygdala (IL) and the basolateral amygdala (BLA) are significantly associated with negative emotions and pain, and they are known to have reciprocal connections. However, the role of IL-BLA circuit pathways in neuropathic pain-induced anxiety and depression remains unexplored. Electroacupuncture (EA) is frequently employed in the treatment of chronic pain and emotional disorders. However, The mechanism by which EA mediates its analgesic and emotion-alleviating effects via the IL-BLA circuit remains uncertain. Here, we used chemogenetic manipulation combined with behavioral tests to detect pain induced anxiety-like and depression-like behaviors. We observed that activation of the IL-BLA circuit by chemogenetic activation induced depression-like behavior of mice. Additionally, we discovered that chemogenetic activation of the IL-BLA circuit successfully prevented the beneficial effects of EA on depression-like behavior brought on by chronic pain in mice with spared nerve injury (SNI). We discovered that SNI-induced depression-like behavior could be mitigated by inhibiting the circuit, and EA had a comparable depressive-relieving effect. Furthermore, the IL-BLA circuit's activation or inhibition had no effect on the anxiety-like feelings brought on by SNI. Overall, our findings identify a specific neural circuit that selectively regulates pain-induced depression-like emotions, without affecting pain-induced anxiety-like emotions. This discovery offers a precise target for future treatments of comorbid pain and depression and provides a plausible explanation for the efficacy of EA in treating depression-like emotions associated with chronic pain.http://www.sciencedirect.com/science/article/pii/S0361923024002260Neuropathic painDepressionElectroacupunctureIL-BLA ciruitNeuronal projection
spellingShingle Yiping Xie
Zui Shen
Xixiao Zhu
Yushuang Pan
Haiju Sun
Mengdi Xie
Qiuzhu Gong
Qunqi Hu
Jie Chen
Zemin Wu
Shuting Zhou
Boyu Liu
Xiaofen He
Boyi Liu
Xiaomei Shao
Jianqiao Fang
Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
Brain Research Bulletin
Neuropathic pain
Depression
Electroacupuncture
IL-BLA ciruit
Neuronal projection
title Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
title_full Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
title_fullStr Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
title_full_unstemmed Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
title_short Infralimbic-basolateral amygdala circuit associated with depression-like not anxiety-like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
title_sort infralimbic basolateral amygdala circuit associated with depression like not anxiety like behaviors induced by chronic neuropathic pain and the antidepressant effects of electroacupuncture
topic Neuropathic pain
Depression
Electroacupuncture
IL-BLA ciruit
Neuronal projection
url http://www.sciencedirect.com/science/article/pii/S0361923024002260
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