Related Experiment Video
Updated: Feb 1, 2026
In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor GM-CSF-producing T Helper THGM Cells
Published on: September 10, 2018
Granulocyte-macrophage colony-stimulating factor receptor expression in clinical pain disorder tissues and role in
Philippe Donatien1, Uma Anand1,2, Yiangos Yiangou1
1Peripheral Neuropathy Unit, Centre for Clinical Translation, Department of Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom.
Introduction:
Granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is highly expressed in peripheral macrophages and microglia, and is involved in arthritis and cancer pain in animal models. However, there is limited information on GM-CSFR expression in human central nervous system (CNS), peripheral nerves, or dorsal root ganglia (DRG), particularly in chronic pain conditions.
Objectives:
Immunohistochemistry was used to quantify GM-CSFR expression levels in human tissues, and functional sensory effects of GM-CSF were studied in cultured DRG neurons.
Results:
Granulocyte-macrophage colony-stimulating factor receptor was markedly increased in microglia at lesional sites of multiple sclerosis spinal cords (P = 0.01), which co-localised with macrophage marker CD68 (P = 0.009). In human DRG, GM-CSFR was expressed in a subset of small/medium diameter cells (30%) and few large cells (10%), with no significant change in avulsion-injured DRG. In peripheral nerves, there was a marked decrease in axonal GM-CSFR after chronic painful nerve injury (P = 0.004) and in painful neuromas (P = 0.0043); CD-68-positive macrophages were increased (P = 0.017) but did not appear to express GM-CSFR. Although control synovium showed absent GM-CSFR immunostaining, this was markedly increased in macrophages of painful osteoarthritis knee synovium. Granulocyte-macrophage colony-stimulating factor receptor was expressed in 17 ± 1.7% of small-/medium-sized cultured adult rat DRG neurons, and in 27 ± 3.3% of TRPV1-positive neurons. Granulocyte-macrophage colony-stimulating factor treatment sensitized capsaicin responses in vitro, which were diminished by p38 MAPK or TrkA inhibitors.
Conclusion:
Our findings support GM-CSFR as a therapeutic target for pain and hypersensitivity in clinical CNS and peripheral inflammatory conditions. Although GM-CSFR was decreased in chronic painful injured peripheral nerves, it could mediate CNS neuroinflammatory effects, which deserves study.
Insights
Granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is increased in inflammatory conditions like multiple sclerosis and osteoarthritis, suggesting it as a therapeutic target for pain. However, GM-CSFR decreases in injured peripheral nerves.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is implicated in pain pathways and inflammation in animal models.
- Limited data exists on GM-CSFR expression in human central nervous system (CNS), peripheral nerves, and dorsal root ganglia (DRG), especially in chronic pain states.
Purpose of the Study:
- To investigate GM-CSFR expression in human CNS, peripheral nerves, and DRG.
- To explore the functional role of GM-CSF in sensory neurons and its potential as a therapeutic target for pain.
Main Methods:
- Immunohistochemistry was employed to quantify GM-CSFR levels in human tissues, including spinal cords, DRG, peripheral nerves, and synovium.
- Functional studies involved cultured adult rat DRG neurons, assessing responses to GM-CSF and the effects of inhibitors (p38 MAPK, TrkA).
Main Results:
- GM-CSFR was significantly elevated in microglia at lesional sites in multiple sclerosis spinal cords and in macrophages of painful osteoarthritis synovium.
- In human DRG, GM-CSFR was found in a subset of small/medium neurons, with no change in avulsion-injured DRG.
- Peripheral nerves showed decreased axonal GM-CSFR after chronic painful injury and in neuromas, despite increased macrophages.
- GM-CSF treatment sensitized cultured DRG neurons' responses to capsaicin, an effect reduced by p38 MAPK or TrkA inhibition.
Conclusions:
- GM-CSFR is a potential therapeutic target for pain and hypersensitivity in CNS and peripheral inflammatory conditions.
- Despite decreased expression in injured peripheral nerves, GM-CSFR's role in CNS neuroinflammation warrants further investigation.
More Related Videos
06:46Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
12:02Isolation of Exosome-Enriched Extracellular Vesicles Carrying Granulocyte-Macrophage Colony-Stimulating Factor from Embryonic Stem Cells
Published on: November 11, 2021
Related Concept Videos
01:28Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...
01:28Disorders of the Nervous Tissue
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...
01:19The Role of Ion Channels in Neuronal Computation
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
02:16Transcription Factors
02:18Intrinsically Disordered Proteins
01:30Factors Affecting Drug Distribution: Tissue Permeability
Small molecules with a molecular weight below 500 to 600 Daltons can easily pass through the capillary membrane, gaining access to different tissues. Larger...