ArticleThe Journal of biological chemistry2012
Estrogen facilitates spinal cord synaptic transmission via membrane-bound estrogen receptors: implications for pain hypersensitivity.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Temporal Transcriptomic Changes in the Cingulate Cortex of Neuropathic Pain Mice.Biomedicines · 2026Article
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- Acute Administration of Ampakine CX1739 after Cervical Spinal Cord Injury.Journal of neurotrauma · 2026Article
- Medical Treatment for Endometriosis: One Size Does Not Fit All.Journal of clinical medicine · 2026Review
- Impact of Menopause and Associated Hormonal Changes on Spine Health in Older Females: A Review.Cells · 2026Review
- Article
- Dysregulation of Hedonic Processing in Chronic Pain: Insights from Preclinical Data.Brain sciences · 2025Review
- Multimorbidity Patterns and Depression: Bridging Epidemiological Associations with Predictive Analytics for Risk Stratification.Healthcare (Basel, Switzerland) · 2025Article
- From neurotoxicity to neuroprotection: Rethinking GABACell biology and toxicology · 2025Review
- Review
- Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies.International journal of molecular sciences · 2023Review
- A transcriptome dataset for gonadectomy-induced changes in rat spinal cord.Scientific data · 2022Article
- Estrogen Up-Regulates Iron Transporters and Iron Storage Protein Through Hypoxia Inducible Factor 1 Alpha Activation Mediated by Estrogen Receptor β and G Protein Estrogen Receptor in BV2 Microglia Cells.Neurochemical research · 2022Article
- Estrogen metabolites increase nociceptor hyperactivity in a mouse model of uterine pain.JCI insight · 2022Article
- Estrogen receptor β/substance P signaling in spinal cord mediates antinociceptive effect in a mouse model of discogenic low back pain.Frontiers in cellular neuroscience · 2022Article
- Brain-derived estrogen and neural function.Neuroscience and biobehavioral reviews · 2022Review
- Estrogen receptor alpha, G-protein coupled estrogen receptor 1, and aromatase: Developmental, sex, and region-specific differences across the rat caudate-putamen, nucleus accumbens core and shell.The Journal of comparative neurology · 2021Article
- Progesterone and Allopregnanolone Rapidly Attenuate Estrogen-Associated Mechanical Allodynia in Rats with Persistent Temporomandibular Joint Inflammation.Frontiers in integrative neuroscience · 2020Article
- G Protein-Coupled Estrogen Receptor Immunoreactivity Fluctuates During the Estrous Cycle and Show Sex Differences in the Amygdala and Dorsal Hippocampus.Frontiers in endocrinology · 2020Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence suggests that estrogen is synthesized in the spinal dorsal horn and plays a role in nociceptive processes. However, the cellular and molecular mechanisms underlying these effects remain unclear. Using electrophysiological, biochemical, and morphological techniques, we here demonstrate that 17β-estradiol (E2), a major form of estrogen, can directly modulate spinal cord synaptic transmission by 1) enhancing NMDA receptor-mediated synaptic transmission in dorsal horn neurons, 2) increasing glutamate release from primary afferent terminals, 3) increasing dendritic spine density in cultured spinal cord dorsal horn neurons, and 4) potentiating spinal cord long term potentiation (LTP) evoked by high frequency stimulation (HFS) of Lissauer's tract. Notably, E2-BSA, a ligand that acts only on membrane estrogen receptors, can mimic E2-induced facilitation of HFS-LTP, suggesting a nongenomic action of this neurosteroid. Consistently, cell surface biotinylation demonstrated that three types of ERs (ERα, ERβ, and GPER1) are localized on the plasma membrane of dorsal horn neurons. Furthermore, the ERα and ERβ antagonist ICI 182,780 completely abrogates the E2-induced facilitation of LTP. ERβ (but not ERα) activation can recapitulate E2-induced persistent increases in synaptic transmission (NMDA-dependent) and dendritic spine density, indicating a critical role of ERβ in spinal synaptic plasticity. E2 also increases the phosphorylation of ERK, PKA, and NR2B, and spinal HFS-LTP is prevented by blockade of PKA, ERK, or NR2B activation. Finally, HFS increases E2 release in spinal cord slices, which can be prevented by aromatase inhibitor androstatrienedione, suggesting activity-dependent local synthesis and release of endogenous E2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.