ArticleThe Journal of clinical investigation2023
Molecular identification of bulbospinal ON neurons by GPER, which drives pain and morphine tolerance.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Morphine Tolerance Gated through EZH2-Mediated Suppression of Trpc5 in Spinal GABAergic Interneurons in Male Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spinal and supraspinal mechanisms of chronic itch: from neuronal circuits to the neuro-immune-microbial axis.Frontiers in medicine · 2026Review
- Reviewing the Peripheral and Central Mechanisms of Visceral Hypersensitivity in Intestinal Disorders.International journal of medical sciences · 2026Review
- Article
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice.Nature communications · 2025Article
- Network pharmacology approach to unveiling the mechanism of berberine in the amelioration of morphine tolerance.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Electroacupuncture produces analgesic effects via cannabinoid CB1 receptor-mediated GABAergic neuronal inhibition in the rostral ventromedial medulla.Chinese medicine · 2025Article
- GPER Enhances Chronic Burn Pain via PKC-Mediated Mu-Opioid Receptor Phosphorylation in the Rostral Ventromedial Medulla.Journal of pain research · 2025Article
- The role of gonadal hormones in regulating opioid antinociception.Annals of medicine · 2024Review
- A brain-to-liver signal mediates the inhibition of liver regeneration under chronic stress in mice.Nature communications · 2024Article
- Multidimensional Analgesia of Acupuncture by Increasing Expression of MD2 in Central Nervous System.Chinese journal of integrative medicine · 2024Article
- Morphine-responsive neurons that regulate mechanical antinociception.Science (New York, N.Y.) · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- The 'in's and out's' of descending pain modulation from the rostral ventromedial medulla.Trends in neurosciences · 2024Review
- Effect of astrocyte GPER on the optic nerve inflammatory response following optic nerve injury in mice.Heliyon · 2024Article
- Cell type-specific dissection of sensory pathways involved in descending modulation.Trends in neurosciences · 2023Review
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies.International journal of molecular sciences · 2023Review
- Bulbospinal nociceptive ON and OFF cells related neural circuits and transmitters.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 2 countries.
Funding
Abstract
The rostral ventromedial medulla (RVM) exerts bidirectional descending modulation of pain attributable to the activity of electrophysiologically identified pronociceptive ON and antinociceptive OFF neurons. Here, we report that GABAergic ON neurons specifically express G protein-coupled estrogen receptor (GPER). GPER+ neurons exhibited characteristic ON-like responses upon peripheral nociceptive stimulation. Optogenetic activation of GPER+ neurons facilitated, but their ablation abrogated, pain. Furthermore, activation of GPER caused depolarization of ON cells, potentiated pain, and ameliorated morphine analgesia through desensitizing μ-type opioid receptor-mediated (MOR-mediated) activation of potassium currents. In contrast, genetic ablation or pharmacological blockade of GPER attenuated pain, enhanced morphine analgesia, and delayed the development of morphine tolerance in diverse preclinical pain models. Our data strongly indicate that GPER is a marker for GABAergic ON cells and illuminate the mechanisms underlying hormonal regulation of pain and analgesia, thus highlighting GPER as a promising target for the treatment of pain and opioid tolerance.
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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.