染料木素通过抑制去卵巢大鼠三叉神经脊髓核ERK1/2信号通路逆转17β-雌二醇对实验性咬合干扰所致慢性咬肌痛觉过敏的加重作用。

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2025-03-24 DOI:10.1016/j.ejphar.2025.177544

Si-Yi Mo , Yuan Li , Ying-Ying Fan , Yao-Jun Zhang , Jing-Wen Liu , Xu-Tong Song , Xiao-Xiang Xu , Ye Cao , Jian-Qiu Jin , Qiu-Fei Xie

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引用次数: 0

摘要

背景：颞下颌紊乱（TMD）疼痛在女性中比男性更普遍，高雌激素水平可能是一个危险因素。研究表明，17β-雌二醇（E2）会加重实验性咬合干扰（EOI）诱导的口面部痛觉过敏，而染料木黄酮可以逆转这一现象。本研究旨在探讨脊髓三叉核（Sp5）内E2加重疼痛的中枢机制和染料木素在eoi诱导的慢性咬痛模型中的抗雌激素作用。方法：雌性大鼠进行卵巢切除术（OVX），然后用染料木素或染料木素（染料木素不抑制蛋白酪氨酸激酶（PTKs）的对照药物）预处理，E2替代和EOI应用。测量双侧咬肌的头退缩阈值（HWTs）来评估疼痛敏感性。p-ERK和两种PTKs (Yes-associated protein， YAP；通过免疫荧光染色和/或Western blotting检测双侧Sp5的Src激酶（Src）。通过鞘内注射（i.t）给药ERK抑制剂PD98059或载体来抑制ERK1/2信号通路。结果：E2增强eoi诱导的OVX大鼠咬肌机械性痛觉过敏，上调双侧Sp5 ERK1/2磷酸化。阻断Sp5中ERK1/2的磷酸化逆转了E2的加重作用。染料木素可能通过抑制双侧Sp5中PTKs和p-ERK1/2的上调，部分逆转E2联合EOI诱导的咬痛症过敏。结论：染料木素通过抑制YAP和Src酪氨酸激酶以及下游Sp5 ERK1/2信号通路，减轻E2对eoi诱导的慢性机械性痛觉过敏的疼痛加重作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Genistein reverses the exacerbating effect of 17β-estradiol on experimental occlusal interference induced chronic masseter hyperalgesia through suppressing ERK1/2 signal pathway in spinal trigeminal nucleus of ovariectomized rats

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Background

Temporomandibular disorder (TMD) pain is more prevalent in females than in males, with high estrogen levels potentially being a risk factor. Research indicates that 17β-estradiol (E2) exacerbates experimental occlusal interference (EOI)-induced orofacial hyperalgesia, which can be reversed by genistein. This study aimed to explore the central mechanisms within the spinal trigeminal nucleus (Sp5) related to the pain-exacerbating effect of E2 and the antiestrogenic properties of genistein in a model of EOI-induced chronic masseter pain.

Methods

Female rats underwent ovariectomy (OVX), followed by pretreatment with genistein or genistin (a control drug for genistein that does not inhibit protein tyrosine kinases (PTKs)), E2 replacement, and EOI application. The head withdrawal thresholds (HWTs) of the bilateral masseters were measured to evaluate pain sensitivity. Expression levels of p-ERK and two PTKs (Yes-associated protein, YAP; Src kinase, Src) in bilateral Sp5 were assessed through immunofluorescent staining and/or Western blotting. The ERK inhibitor PD98059 or vehicle was administered via intrathecal injection (i.t.) to inhibit the ERK1/2 signaling pathway.

Results

E2 intensified EOI-induced masseter mechanical hyperalgesia in OVX rats, and upregulated the phosphorylation of ERK1/2 in bilateral Sp5. Blocking phosphorylation of ERK1/2 in Sp5 reversed the exacerbating effect of E2. Genistein partially reversed the masseter hyperalgesia induced by E2 combined with EOI, possibly through the inhibition of PTKs and p-ERK1/2 upregulation in bilateral Sp5.

Conclusion

Genistein alleviates the pain-exacerbating effect of E2 on EOI-induced chronic mechanical hyperalgesia by inhibiting YAP and Src tyrosine kinases as well as the downstream ERK1/2 signaling pathway in Sp5.

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来源期刊

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.