17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Weste...

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Main Authors: Yun Liu, Xiao-Xiang Xu, Ye Cao, Si-Yi Mo, Shan-Shan Bai, Ying-Ying Fan, Xiao-Yu Zhang, Qiu-Fei Xie
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/13/6945
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author Yun Liu
Xiao-Xiang Xu
Ye Cao
Si-Yi Mo
Shan-Shan Bai
Ying-Ying Fan
Xiao-Yu Zhang
Qiu-Fei Xie
author_facet Yun Liu
Xiao-Xiang Xu
Ye Cao
Si-Yi Mo
Shan-Shan Bai
Ying-Ying Fan
Xiao-Yu Zhang
Qiu-Fei Xie
author_sort Yun Liu
collection DOAJ
description Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.
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spelling doaj.art-4ab0fd0519114adfbfc706580591d5e62023-11-22T02:01:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213694510.3390/ijms2213694517β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized RatsYun Liu0Xiao-Xiang Xu1Ye Cao2Si-Yi Mo3Shan-Shan Bai4Ying-Ying Fan5Xiao-Yu Zhang6Qiu-Fei Xie7Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaCentral Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaPain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.https://www.mdpi.com/1422-0067/22/13/694517β-estradiolexperimental occlusal interferencehyperalgesiatrigeminal ganglionneuronal excitabilityTRPV1
spellingShingle Yun Liu
Xiao-Xiang Xu
Ye Cao
Si-Yi Mo
Shan-Shan Bai
Ying-Ying Fan
Xiao-Yu Zhang
Qiu-Fei Xie
17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats
International Journal of Molecular Sciences
17β-estradiol
experimental occlusal interference
hyperalgesia
trigeminal ganglion
neuronal excitability
TRPV1
title 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats
title_full 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats
title_fullStr 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats
title_full_unstemmed 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats
title_short 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats
title_sort 17β estradiol exacerbated experimental occlusal interference induced chronic masseter hyperalgesia by increasing the neuronal excitability and trpv1 function of trigeminal ganglion in ovariectomized rats
topic 17β-estradiol
experimental occlusal interference
hyperalgesia
trigeminal ganglion
neuronal excitability
TRPV1
url https://www.mdpi.com/1422-0067/22/13/6945
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