Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury
Neuropathic pain is a common cause of chronic pain and is often accompanied by negative emotions, making it complex and difficult to treat. However, the neural circuit mechanisms underlying these symptoms remain unclear. Herein, we present a novel pathway associated with comorbid chronic pain and an...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.757628/full |
| _version_ | 1818942633982033920 |
|---|---|
| author | Xixiao Zhu Yingling Xu Zui Shen Haiyan Zhang Siqi Xiao Yichen Zhu Mengwei Wu Yeqing Chen Zemin Wu Yunyun Xu Xiaofen He Boyu Liu Jinggen Liu Junying Du Jing Sun Jianqiao Fang Xiaomei Shao |
| author_facet | Xixiao Zhu Yingling Xu Zui Shen Haiyan Zhang Siqi Xiao Yichen Zhu Mengwei Wu Yeqing Chen Zemin Wu Yunyun Xu Xiaofen He Boyu Liu Jinggen Liu Junying Du Jing Sun Jianqiao Fang Xiaomei Shao |
| author_sort | Xixiao Zhu |
| collection | DOAJ |
| description | Neuropathic pain is a common cause of chronic pain and is often accompanied by negative emotions, making it complex and difficult to treat. However, the neural circuit mechanisms underlying these symptoms remain unclear. Herein, we present a novel pathway associated with comorbid chronic pain and anxiety. Using chemogenetic methods, we found that activation of glutamatergic projections from the rostral anterior cingulate cortex (rACCGlu) to the ventrolateral periaqueductal gray (vlPAG) induced both hyperalgesia and anxiety-like behaviors in sham mice. Inhibition of the rACCGlu-vlPAG pathway reduced anxiety-like behaviors and hyperalgesia in the spared nerve injury (SNI) mice model; moreover, electroacupuncture (EA) effectively alleviated these symptoms. Investigation of the related mechanisms revealed that the chemogenetic activation of the rACCGlu-vlPAG circuit effectively blocked the analgesic effect of EA in the SNI mice model but did not affect the chronic pain-induced negative emotions. This study revealed a novel pathway, the rACCGlu-vlPAG pathway, that mediates neuropathic pain and pain-induced anxiety. |
| first_indexed | 2024-12-20T07:14:33Z |
| format | Article |
| id | doaj.art-0243de80450d48b78cc63ebb46e6aff4 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-20T07:14:33Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-0243de80450d48b78cc63ebb46e6aff42022-12-21T19:48:49ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-01-011510.3389/fnins.2021.757628757628Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve InjuryXixiao ZhuYingling XuZui ShenHaiyan ZhangSiqi XiaoYichen ZhuMengwei WuYeqing ChenZemin WuYunyun XuXiaofen HeBoyu LiuJinggen LiuJunying DuJing SunJianqiao FangXiaomei ShaoNeuropathic pain is a common cause of chronic pain and is often accompanied by negative emotions, making it complex and difficult to treat. However, the neural circuit mechanisms underlying these symptoms remain unclear. Herein, we present a novel pathway associated with comorbid chronic pain and anxiety. Using chemogenetic methods, we found that activation of glutamatergic projections from the rostral anterior cingulate cortex (rACCGlu) to the ventrolateral periaqueductal gray (vlPAG) induced both hyperalgesia and anxiety-like behaviors in sham mice. Inhibition of the rACCGlu-vlPAG pathway reduced anxiety-like behaviors and hyperalgesia in the spared nerve injury (SNI) mice model; moreover, electroacupuncture (EA) effectively alleviated these symptoms. Investigation of the related mechanisms revealed that the chemogenetic activation of the rACCGlu-vlPAG circuit effectively blocked the analgesic effect of EA in the SNI mice model but did not affect the chronic pain-induced negative emotions. This study revealed a novel pathway, the rACCGlu-vlPAG pathway, that mediates neuropathic pain and pain-induced anxiety.https://www.frontiersin.org/articles/10.3389/fnins.2021.757628/fullchronic painneuropathic painanxietyrostral anterior cingulated cortexperiaqueductal grayelectroacupuncture |
| spellingShingle | Xixiao Zhu Yingling Xu Zui Shen Haiyan Zhang Siqi Xiao Yichen Zhu Mengwei Wu Yeqing Chen Zemin Wu Yunyun Xu Xiaofen He Boyu Liu Jinggen Liu Junying Du Jing Sun Jianqiao Fang Xiaomei Shao Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury Frontiers in Neuroscience chronic pain neuropathic pain anxiety rostral anterior cingulated cortex periaqueductal gray electroacupuncture |
| title | Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury |
| title_full | Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury |
| title_fullStr | Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury |
| title_full_unstemmed | Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury |
| title_short | Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury |
| title_sort | rostral anterior cingulate cortex ventrolateral periaqueductal gray circuit underlies electroacupuncture to alleviate hyperalgesia but not anxiety like behaviors in mice with spared nerve injury |
| topic | chronic pain neuropathic pain anxiety rostral anterior cingulated cortex periaqueductal gray electroacupuncture |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.757628/full |
| work_keys_str_mv | AT xixiaozhu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT yinglingxu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT zuishen rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT haiyanzhang rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT siqixiao rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT yichenzhu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT mengweiwu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT yeqingchen rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT zeminwu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT yunyunxu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT xiaofenhe rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT boyuliu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT jinggenliu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT junyingdu rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT jingsun rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT jianqiaofang rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury AT xiaomeishao rostralanteriorcingulatecortexventrolateralperiaqueductalgraycircuitunderlieselectroacupuncturetoalleviatehyperalgesiabutnotanxietylikebehaviorsinmicewithsparednerveinjury |