ArticleProceedings of the National Academy of Sciences of the United States of America2017
Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- TREM-1-dependent macrophage infiltration mediates visceral hypersensitivity via vlPAG GABAergic neuron activation in a mouse model of inflammatory bowel disease.Cellular & molecular biology letters · 2026Article
- Mechanisms of chronic abdominal pain in inflammatory bowel disease and implications for treatment.Nature reviews. Gastroenterology & hepatology · 2026Review
- Transcriptomic signatures in tetrapartite brain region identifies shared and unique gene signatures for substance-use.Frontiers in cellular neuroscience · 2026Article
- Neuroimmune regulation of visceral pain: roles of microglia, purinergic signaling, and neuroinflammation.Frontiers in immunology · 2026Review
- Microglia-mediated BLA glutamatergic neuronal hyperactivity in the BLA-ACC pathway contributes to stress-induced visceral hypersensitivity and anxiety in rats.Molecular medicine (Cambridge, Mass.) · 2025Article
- Mutations in the human CSF1R gene impact microglia's maintenance of brain white matter integrity.Nature immunology · 2025Article
- Neuroimmune Interactions in the Intestine.Annual review of immunology · 2024Review
- Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review.Frontiers in immunology · 2024Article
- "Sentinel or accomplice": gut microbiota and microglia crosstalk in disorders of gut-brain interaction.Protein & cell · 2023Review
- Article
- Differential regulation of microglial states by colony stimulating factors.Frontiers in cellular neuroscience · 2023Review
- Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease.PloS one · 2023Article
- Modeling CSF-1 receptor deficiency diseases - how close are we?The FEBS journal · 2022Review
- Purinergic Pathways in the Spinal Microglia as a Putative Target for Treatment of Chronic Abdominal Pain.Cellular and molecular gastroenterology and hepatology · 2022Article
- Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.Acta pharmacologica Sinica · 2021Article
- Chronic Abdominal Pain in IBD Research Initiative: Unraveling Biological Mechanisms and Patient Heterogeneity to Personalize Treatment and Improve Clinical Outcomes.Crohn's & colitis 360 · 2021Article
- SCF + G-CSF treatment in the chronic phase of severe TBI enhances axonal sprouting in the spinal cord and synaptic pruning in the hippocampus.Acta neuropathologica communications · 2021Article
- Colony stimulating factors in the nervous system.Seminars in immunology · 2021Review
- Repeated allergic asthma in early versus late pregnancy differentially impacts offspring brain and behavior development.Brain, behavior, and immunity · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.
Indexed as
Identifiers
What OpenQuestion holds
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.