Orofacial pain Scientific Publications

Latest publication 07/05/2025

Genistein reverses the exacerbating effect of 17Beta-estradiol on experimental o

Background Temporomandibular disorder (TMD) pain is more prevalent in females than in males, with high estrogen levels potentially being a risk...

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    [title] => Genistein reverses the exacerbating effect of 17Beta-estradiol on experimental o
    [paragraph] => Genistein reverses the exacerbating effect of 17Beta-estradiol on experimental occlusal interference induced chronic masseter hyperalgesia through suppressing ERK12 signal pathway in spinal trigeminal nucleus of ovariectomized rats
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Authors
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

Lab
Department of Prosthodontics, Center for Oral and Jaw Functional Diagnosis, Treatment and Research, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, PR China
Journal
European Journal of Pharmacology
Abstract
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 17beta-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.
Keywords/Topics
Genistein; 17beta-estradiol; Experimental occlusal interference; Hyperalgesia; Phospho-extracellular signal regulated kinase1/2 (ERK1/2); Protein tyrosine kinases (PTK)
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As an electronic version of the classical Von Frey Filaments esthesiometer (or aesthesiometer), the latest evolution of Bioseb's Electronic Von Frey instrument for determining the mechanical sensitivity threshold in rodents (rats and mice) is a must-have instrument for your reseach on hyperalgesia and allodynia. By measuring and recording the force at which the animal exhibits a paw withdrawal reflex, pathologies related to sensory response and hyper- or hypo-aesthesia can be studied.

The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.

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