Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain
Chronic pain can cause both hyperalgesia and anxiety symptoms. However, how the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing how the two components...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2023-05-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI166356 |
| _version_ | 1827768213671247872 |
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| author | Feng Gao Jie Huang Guo-Bin Huang Qiang-Long You Shan Yao Shen-Ting Zhao Jian Liu Cui-Hong Wu Gui-Fu Chen Shi-Min Liu Zongyan Yu Yan-Ling Zhou Yu-Ping Ning Shenquan Liu Bing-Jie Hu Xiang-Dong Sun |
| author_facet | Feng Gao Jie Huang Guo-Bin Huang Qiang-Long You Shan Yao Shen-Ting Zhao Jian Liu Cui-Hong Wu Gui-Fu Chen Shi-Min Liu Zongyan Yu Yan-Ling Zhou Yu-Ping Ning Shenquan Liu Bing-Jie Hu Xiang-Dong Sun |
| author_sort | Feng Gao |
| collection | DOAJ |
| description | Chronic pain can cause both hyperalgesia and anxiety symptoms. However, how the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing how the two components are encoded. We report that PrL neurons projecting to the basolateral amygdala (PrLBLA) and those projecting to the ventrolateral periaqueductal gray (PrLl/vlPAG) were segregated and displayed elevated and reduced neuronal activity, respectively, during pain chronicity. Consistently, optogenetic suppression of the PrL-BLA circuit reversed anxiety-like behaviors, whereas activation of the PrL-l/vlPAG circuit attenuated hyperalgesia in mice with chronic pain. Moreover, mechanistic studies indicated that elevated TNF-α/TNFR1 signaling in the PrL caused increased insertion of GluA1 receptors into PrLBLA neurons and contributed to anxiety-like behaviors in mice with chronic pain. Together, these results provide insights into the circuit and molecular mechanisms in the PrL for controlling pain-related hyperalgesia and anxiety-like behaviors. |
| first_indexed | 2024-03-11T12:09:11Z |
| format | Article |
| id | doaj.art-d3f04cad1c8e4cd585eb54e45f1c69a6 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:09:11Z |
| publishDate | 2023-05-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-d3f04cad1c8e4cd585eb54e45f1c69a62023-11-07T16:20:16ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-05-011339Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic painFeng GaoJie HuangGuo-Bin HuangQiang-Long YouShan YaoShen-Ting ZhaoJian LiuCui-Hong WuGui-Fu ChenShi-Min LiuZongyan YuYan-Ling ZhouYu-Ping NingShenquan LiuBing-Jie HuXiang-Dong SunChronic pain can cause both hyperalgesia and anxiety symptoms. However, how the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing how the two components are encoded. We report that PrL neurons projecting to the basolateral amygdala (PrLBLA) and those projecting to the ventrolateral periaqueductal gray (PrLl/vlPAG) were segregated and displayed elevated and reduced neuronal activity, respectively, during pain chronicity. Consistently, optogenetic suppression of the PrL-BLA circuit reversed anxiety-like behaviors, whereas activation of the PrL-l/vlPAG circuit attenuated hyperalgesia in mice with chronic pain. Moreover, mechanistic studies indicated that elevated TNF-α/TNFR1 signaling in the PrL caused increased insertion of GluA1 receptors into PrLBLA neurons and contributed to anxiety-like behaviors in mice with chronic pain. Together, these results provide insights into the circuit and molecular mechanisms in the PrL for controlling pain-related hyperalgesia and anxiety-like behaviors.https://doi.org/10.1172/JCI166356Neuroscience |
| spellingShingle | Feng Gao Jie Huang Guo-Bin Huang Qiang-Long You Shan Yao Shen-Ting Zhao Jian Liu Cui-Hong Wu Gui-Fu Chen Shi-Min Liu Zongyan Yu Yan-Ling Zhou Yu-Ping Ning Shenquan Liu Bing-Jie Hu Xiang-Dong Sun Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain The Journal of Clinical Investigation Neuroscience |
| title | Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain |
| title_full | Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain |
| title_fullStr | Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain |
| title_full_unstemmed | Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain |
| title_short | Elevated prelimbic cortex-to-basolateral amygdala circuit activity mediates comorbid anxiety-like behaviors associated with chronic pain |
| title_sort | elevated prelimbic cortex to basolateral amygdala circuit activity mediates comorbid anxiety like behaviors associated with chronic pain |
| topic | Neuroscience |
| url | https://doi.org/10.1172/JCI166356 |
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