ArticleMolecular pharmacology2013
Brain-derived neurotrophic factor-mediated downregulation of brainstem K+-Cl- cotransporter and cell-type-specific GABA impairment for activation of descending pain facilitation.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Brain-derived neurotrophic factor in fibromyalgia: A systematic review and meta-analysis of its role as a potential biomarker.PloS one · 2023Pooled it
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- Paclitaxel-induced adverse effects: insights into multi-organ toxicities and molecular mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Optogenetic stimulation attenuates central post-stroke pain via BDNF/TrkB signaling pathway modulation in the ascending pain modulation system.Scientific reports · 2025Article
- Association between BDNF/CB1R expression and postoperative pain and recovery in patients with preoperative sleep disorders.BMC anesthesiology · 2025Article
- Co-administration of low-dose-Naltrexone and Carbamazepine remarkedly ameliorate allodynia and cognitive deficit in a rat model of trigeminal neuralgia.Scientific reports · 2025Article
- BDNF Signaling and Pain Modulation.Cells · 2025Review
- Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.International journal of molecular sciences · 2024Review
- The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation.Biomolecules · 2024Review
- BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges.Brain and behavior · 2023Review
- Neonatal inflammation increases hippocampal KCC2 expression through methylation-mediated TGF-β1 downregulation leading to impaired hippocampal cognitive function and synaptic plasticity in adult mice.Journal of neuroinflammation · 2023Article
- The Therapeutic Potential of Neuronal K-Cl Co-Transporter KCC2 in Huntington's Disease and Its Comorbidities.International journal of molecular sciences · 2020Review
- A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression.Neuropsychiatric disease and treatment · 2020Article
- Descending Control Mechanisms and Chronic Pain.Current rheumatology reports · 2019Review
- Differential Neuroplastic Changes in Fibromyalgia and Depression Indexed by Up-Regulation of Motor Cortex Inhibition and Disinhibition of the Descending Pain System: An Exploratory Study.Frontiers in human neuroscience · 2019Article
- Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal KBioMed research international · 2019Review
- Potency of descending pain modulatory system is linked with peripheral sensory dysfunction in fibromyalgia: An exploratory study.Medicine · 2019Observational
- Dexmedetomidine attenuates persistent postsurgical pain by upregulating KJournal of pain research · 2018Article
- Article
- Compensatory Activation of Cannabinoid CB2 Receptor Inhibition of GABA Release in the Rostral Ventromedial Medulla in Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic pain is thought to be partly caused by a loss of GABAergic inhibition and resultant neuronal hyperactivation in the central pain-modulating system, but the underlying mechanisms for pain-modulating neurons in the brain are unclear. In this study, we investigated the cellular mechanisms for activation of brainstem descending pain facilitation in rats under persistent pain conditions. In the nucleus raphe magnus (NRM), a critical relay in the brain's descending pain-modulating system, persistent inflammatory pain induced by complete Freund's adjuvant decreased the protein level of K(+)-Cl(-) cotransporter (KCC2) in both total and synaptosomal preparations. Persistent pain also shifted the equilibrium potential of GABAergic inhibitory postsynaptic current (EIPSC) to a more positive level and increased the firing of evoked action potentials selectively in μ-opioid receptor (MOR)-expressing NRM neurons, but not in MOR-lacking NRM neurons. Microinjection of brain-derived neurotrophic factor (BDNF) into the NRM inhibited the KCC2 protein level in the NRM, and both BDNF administration and KCC2 inhibition by furosemide mimicked the pain-induced effects on EIPSC and excitability in MOR-expressing neurons. Furthermore, inhibiting BDNF signaling by NRM infusion of tyrosine receptor kinase B-IgG or blocking KCC2 with furosemide prevented these pain effects in MOR-expressing neurons. These findings demonstrate a cellular mechanism by which the hyperactivity of NRM MOR-expressing neurons, presumably responsible for descending pain facilitation, contributes to pain sensitization through the signaling cascade of BDNF-KCC2-GABA impairment in the development of chronic pain.
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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.