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

Abstract
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.
AuthorsYun Liu, Xiao-Xiang Xu, Ye Cao, Si-Yi Mo, Shan-Shan Bai, Ying-Ying Fan, Xiao-Yu Zhang, Qiu-Fei Xie
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 13 (Jun 28 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34203300 (Publication Type: Journal Article)
Chemical References
  • 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
  • Acrylamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • TRPV Cation Channels
  • TRPV1 receptor
  • Estradiol
Topics
  • Acrylamides (pharmacology)
  • Animals
  • Blotting, Western
  • Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
  • Estradiol (genetics, metabolism)
  • Female
  • Fluorescent Antibody Technique
  • Hyperalgesia (drug therapy, metabolism)
  • Neurons, Afferent (drug effects)
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • TRPV Cation Channels (metabolism)
  • Trigeminal Ganglion (drug effects, metabolism)

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