ArticlePloS one2017
Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 53 citations in OpenAlex.
- Sex-Specific Mechanisms of Central Sensitization: A Narrative Review of the Neuroimmune Architecture of Chronic Pain.Cureus · 2026Review
- Natural antisense transcript Nat9a suppresses Scn9a (NaScientific reports · 2026Article
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Sodium channels as a new target for pain treatment.Frontiers in pharmacology · 2025Review
- Article
- The Temporomandibular Joint and the Human Body: A New Perspective on Cross Talk.Dentistry journal · 2024Review
- Estrogen Hormones' Implications on the Physiopathology of Temporomandibular Dysfunction.Journal of clinical medicine · 2024Review
- The effect of sex and estrus cycle stage on optogenetic spreading depression induced migraine-like pain phenotypes.The journal of headache and pain · 2023Article
- Article
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- The degeneration-pain relationship in the temporomandibular joint: Current understandings and rodent models.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- [Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter- ference-induced chronic masseter hyperalgesia in ovariectomized rats].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
- Prevalence of Temporomandibular Disorder-Related Pain among Adults Seeking Dental Care: A Cross-Sectional Study.International journal of dentistry · 2022Article
- The role of mechanosensitive ion channels in the gastrointestinal tract.Frontiers in physiology · 2022Review
- Preclinical models of deep craniofacial nociception and temporomandibular disorder pain.The Japanese dental science review · 2021Review
- Hormonal influences in migraine - interactions of oestrogen, oxytocin and CGRP.Nature reviews. Neurology · 2021Review
- TMD in Females with Menstrual Disorders.International journal of environmental research and public health · 2021Article
- 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 · 2021Article
- Role of Connexin 43 in an Inflammatory Model for TMJ Hyperalgesia.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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Abstract
backgroundTemporomandibular disorders (TMDs) have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7) plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG) is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ). Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored.
methodsEstrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ), the G protein coupled estrogen receptor (GPR30), and Nav1.7 in TG were examined using immunohistofluorescence.
resultsUpregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1.7 expression and head withdrawal threshold in ovariectomized rats. ERα and ERβ, but not GPR30, were mostly co-localized with Nav1.7 in neurons in TG. In the nerve growth factor-induced and ERα-transfected PC12 cells, 17β-estradiol dose-dependently enhanced Nav1.7 promoter activity, whereas mutations of the estrogen response element at -1269/-1282 and -1214/-1227 in the promoter completely abolished its effect on the promoter activity.
conclusionEstradiol could upregulate trigeminal ganglionic Nav1.7 expression to contribute to hyperalgesia of inflamed TMJ.
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