Central Sensitization-Related Changes in Brain Function Activity in a Rat Endometriosis-Associated Pain Model

Ping Zheng; Shuangzheng Jia; Dalong Guo; Sikai Chen; Wen Zhang; Aoshuang Cheng; Weijie Xie; Guibo Sun; Jinhua Leng; Jinghe Lang

doi:10.2147/JPR.S232313

Central Sensitization-Related Changes in Brain Function Activity in a Rat Endometriosis-Associated Pain Model

J Pain Res. 2020 Jan 13:13:95-107. doi: 10.2147/JPR.S232313. eCollection 2020.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
² Air Force Medical Center, PLA, Beijing, People's Republic of China.
³ Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, People's Republic of China.

Abstract

Background: Pain sensitization processing in the central nervous system may be related to endometriosis-associated pain in patients. The purpose of this study was to understand the alterations in the abnormal pain response in central brain areas and explore the central sensitization mechanism of endometriosis-associated pain.

Methods: An endometriosis model was established in 40 Sprague-Dawley rats, and the rats underwent pain model assessment through behavioral tests. Twenty Sprague-Dawley rats underwent a sham operation as the control group. Thirteen pain rats and 8 control rats received Rs-fMRI examination to explore the brain functional activity areas, and the regional homogeneity (ReHo) method was used to analyze relevant functional signals among the whole brain. The states of neurons and expression of TRPV1 and NMDRA located in the abnormal ReHo signal brain regions were observed using Nissl staining, qRT-PCR and immunohistochemistry.

Results: The rats were divided into a pain group and a control group based on the different syndromes and behavioral assessments. We detected significant enhancement of ReHo signals in the anterior cingulate cortex, hippocampus, and thalamus and a reduction in the ReHo values in the basomedial amygdaloid nucleus (BM) and primary motor cortex (M1) in the pain rat group via Rs-fMRI examination. The number of Nissl bodies and apoptotic neurons was increased; moreover, the volume of neurons increased compensatorily in the cingulate cortex, thalamus and hippocampus in the pain group. TRPV1 and NMDRA were overexpressed in apoptotic neurons in the higher ReHo value brain regions in the endometriosis pain group.

Conclusion: These findings suggest that in rats with endometriosis-associated pain, ReHo signal enhancement was observed in the cingulate cortex, thalamus and hippocampus, which may be due to the increase in the number of apoptotic neurons or the compensatory increase in the volume of overactive neurons.

Keywords: NMDRA; Rs-fMRI; TRPV1; behavioral assessment; central sensitization; endometriosis-associated pain; rat model; regional homogeneity.