The chronification mechanism of orofacial inflammatory pain: Facilitation by GPER1 and microglia in the rostral ventral medulla

作者全名："Zheng, Wenwen; Huang, Xilu; Wang, Jing; Gao, Feng; Chai, Zhaowu; Zeng, Jie; Li, Sisi; Yu, Cong"

作者地址："[Zheng, Wenwen; Huang, Xilu; Wang, Jing; Chai, Zhaowu; Zeng, Jie; Li, Sisi; Yu, Cong] Chongqing Med Univ, Affiliated Hosp Stomatol, Chongqing, Peoples R China; [Gao, Feng] Sixth Peoples Hosp Chongqing, Anesthesiol, Chongqing, Peoples R China"

通信作者："Yu, C (通讯作者)，Chongqing Med Univ, Affiliated Hosp Stomatol, Chongqing, Peoples R China."

来源：FRONTIERS IN MOLECULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000916482600001

JCR分区：Q2

影响因子：3.5

年份：2023

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：chronic orofacial pain; GPER1; microglia; GluA1; neuroplasticity

摘要："BackgroundChronic orofacial pain is a common and incompletely defined clinical condition. The role of G protein-coupled estrogen receptor 1 (GPER1) as a new estrogen receptor in trunk and visceral pain regulation is well known. Here, we researched the role of GPER1 in the rostral ventral medulla (RVM) during chronic orofacial pain. Methods and ResultsA pain model was established where rats were injected in the temporomandibular joint with complete Freund's adjuvant (CFA) to simulate chronic orofacial pain. Following this a behavioral test was performed to establish pain threshold and results showed that the rats injected with CFA had abnormal pain in the orofacial regions. Additional Immunostaining and blot analysis indicated that microglia were activated in the RVM and GPER1 and c-Fos were significantly upregulated in the rats. Conversely, when the rats were injected with G15 (a GPER1 inhibitor) the abnormal pain the CFA rats were experiencing was alleviated and microglia activation was prevented. In addition, we found that G15 downregulated the expression of phospholipase C (PLC) and protein kinase C (PKC), inhibited the expression of GluA1, restores aberrant synaptic plasticity and reduces the overexpression of the synapse-associated proteins PSD-95 and syb-2 in the RVM of CFA rats. ConclusionThe findings indicate that GPER1 mediates chronic orofacial pain through modulation of the PLC-PKC signal pathway, sensitization of the RVM region and enhancement of neural plasticity. These results of this study therefore suggest that GPER1 may serve as a potential therapeutic target for chronic orofacial pain."

基金机构："CSA Clinical Research Fund [CSA-A2021-05]; Chongqing Health Commission and Science and Technology Bureau Chongqing, China [2021MSXM188]"

基金资助正文："This work was supported by CSA Clinical Research Fund (CSA-A2021-05) and the joint project of Chongqing Health Commission and Science and Technology Bureau Chongqing, China (Grant No. 2021MSXM188)."