ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.
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Who cites it
245 citing papers in PubMed, 472 citations in OpenAlex.
- Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice.Proceedings of the National Academy of Sciences of the United States of America · 2012Trial
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- A JNK-Regulated and IL-1β-Dependent Astrocyte-Neuron Signaling Pathway in the Spinal Dorsal Horn is Essential for Stress-Induced Hyperalgesia.Neural plasticity · 2026Article
- The central regulatory network of cough: a cornerstone of cough management.Journal of thoracic disease · 2025Review
- Polyethylene terephthalate nanoplastics-induced neurotoxicity in adult male Swiss albino mice with amelioration of betaine: a histopathological, neurochemical, and molecular investigation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- GPR37L1 identifies spinal cord astrocytes and protects neuropathic pain after nerve injury.Neuron · 2025Article
- Molecular Anatomy of Synaptic and Extrasynaptic Neurotransmission Between Nociceptive Primary Afferents and Spinal Dorsal Horn Neurons.International journal of molecular sciences · 2025Review
- mGluR5-mediated astrocytes hyperactivity in the anterior cingulate cortex contributes to neuropathic pain in male mice.Communications biology · 2025Article
- Electroacupuncture Inhibits NLRP3-Mediated Microglial Pyroptosis to Ameliorate Chronic Neuropathic Pain in Rats.Journal of pain research · 2025Article
- Pharmacological Network Analysis of the Functions and Mechanism of Quercetin From Jisuikang (JSK) in Spinal Cord Injury (SCI).Journal of cellular and molecular medicine · 2024Article
- Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice.Acta pharmaceutica Sinica. B · 2024Article
- Sigma-1 receptor targeting inhibits connexin 43 based intercellular communication in chronic neuropathic pain.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Immunity impacts cognitive deficits across neurological disorders.Journal of neurochemistry · 2024Review
- FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
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- Astrocytes in preoptic area regulate acute nociception-induced hypothermia through adenosine receptors.CNS neuroscience & therapeutics · 2024Article
- URB937 Prevents the Development of Mechanical Allodynia in Male Rats with Trigeminal Neuralgia.Pharmaceuticals (Basel, Switzerland) · 2023Article
- BDNF/TrkB Signaling Inhibition Suppresses Astrogliosis and Alleviates Mechanical Allodynia in a Partial Crush Injury Model.Experimental neurobiology · 2023Article
185 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The emerging literature implicates a role for glia/cytokines in persistent pain. However, the mechanisms by which these non-neural elements contribute to CNS activity-dependent plasticity and pain are unclear. Using a trigeminal model of inflammatory hyperalgesia, here we provide evidence that demonstrates a mechanism by which glia interact with neurons, leading to activity-dependent plasticity and hyperalgesia. In response to masseter inflammation, there was an upregulation of glial fibrillary acidic proteins (GFAPs), a marker of astroglia, and interleukin-1beta (IL-1beta), a prototype proinflammatory cytokine, in the region of the trigeminal nucleus specifically related to the processing of deep orofacial input. The activated astroglia exhibited hypertrophy and an increased level of connexin 43, an astroglial gap junction protein. The upregulated IL-1beta was selectively localized to astrocytes but not to microglia and neurons. Local anesthesia of the masseter nerve prevented the increase in GFAP and IL-1beta after inflammation, and substance P, a prototype neurotransmitter of primary afferents, induced similar increases in GFAP and IL-1beta, which was blocked by a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester. Injection of IL-1 receptor antagonist and fluorocitrate, a glial inhibitor, attenuated hyperalgesia and NMDA receptor phosphorylation after inflammation. In vitro application of IL-1beta induced NR1 phosphorylation, which was blocked by an IL-1 receptor antagonist, a PKC inhibitor (chelerythrine), an IP3 receptor inhibitor (2-aminoethoxydiphenylborate), and inhibitors of phospholipase C [1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione] and phospholipase A2 (arachidonyltrifluoromethyl ketone). These findings provide evidence of astroglial activation by tissue injury, concomitant IL-1beta induction, and the coupling of NMDA receptor phosphorylation through IL-1 receptor signaling.
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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.