ArticlePain2008
Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat.
Article in Pain, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 94 citations in OpenAlex.
- Chronic joint pain drives sex-specific changes in hippocampal glutamatergic signaling and sleep.npj biomedical innovations · 2026Article
- Mechanisms of chronic abdominal pain in inflammatory bowel disease and implications for treatment.Nature reviews. Gastroenterology & hepatology · 2026Review
- Metabotropic NMDAR Signaling Contributes to Sex Differences in Synaptic Plasticity and Episodic Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The influence of sex on neuroimmune communication, pain, and physiology.Biology of sex differences · 2024Review
- Ovariectomy Exacerbates Acute Ethanol-Induced Tachycardia: Role of Nitric Oxide and NMDA Receptors in the Rostral Ventrolateral Medulla.International journal of molecular sciences · 2023Article
- Roles of Phosphorylation of N-Methyl-D-Aspartate Receptor in Chronic Pain.Cellular and molecular neurobiology · 2023Review
- Phase-specific differential regulation of mechanical allodynia in a murine model of neuropathic pain by progesterone.Frontiers in pharmacology · 2023Article
- Article
- Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain.Brain : a journal of neurology · 2022Article
- Estrogen receptors in pain modulation: cellular signaling.Biology of sex differences · 2021Review
- Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation.Molecular brain · 2020Article
- An Investigation of the Molecular Mechanisms Underlying the Analgesic Effect of Jakyak-Gamcho Decoction: A Network Pharmacology Study.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- "International journal of molecular sciences · 2019Review
- Bisphenol A Regulates Sodium Ramp Currents in Mouse Dorsal Root Ganglion Neurons and Increases Nociception.Scientific reports · 2019Article
- Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats.The journal of pain · 2018Article
- Mechanisms of Stress-induced Visceral Pain.Journal of neurogastroenterology and motility · 2018Review
- Ethanol Enhances Estrogen Mediated Angiogenesis in Breast Cancer.Journal of Cancer · 2018Article
- Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats.Neural regeneration research · 2017Article
- Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin.Frontiers in systems neuroscience · 2017Review
- Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain.Translational psychiatry · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pain symptoms in several chronic pain disorders in women, including irritable bowel syndrome, fluctuate with the menstrual cycle suggesting a gonadal hormone component. In female rats, estrogens modulate visceral sensitivity although the underlying mechanism(s) are unknown. In the present study the effects of 17-beta estradiol on N-methyl-D-aspartate (NMDA) receptor signaling of colorectal nociceptive processing in the spinal cord were examined. Estrogen receptor alpha and the NR1 subunit of the NMDA receptor are co-expressed in dorsal horn neurons, supporting a direct action of estradiol on NMDA receptors. Intrathecal administration of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (APV) dose-dependently attenuated the visceromotor response with greater potency in ovariectomized (OVx) rats compared to OVx with estradiol replacement (E2) rats. Estradiol significantly increased protein expression of NR1 in the lumbosacral spinal cord compared to OVx rats. Colorectal distention significantly increased phosphorylation of NR1ser-897, a PKA phosphorylation site on the NR1 subunit in E2, but not OVx rats. Intrathecal administration of a PKA inhibitor significantly attenuated the visceromotor response, decreased NR1 phosphorylation and increased the potency of APV to attenuate the visceromotor response compared to vehicle-treated E2 rats. These data suggest that estradiol increases spinal processing of visceral nociception by increasing NMDA receptor NR1 subunit expression and increasing site-specific receptor phosphorylation on the NR1 subunit contributing to an increase in NMDA receptor activity.
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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.