Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis. 2897 41

Crohn disease (CD) is a chronic inflammatory disease which progressively affects the digestive tract with unknown etiology. During the disease course, intestinal fibrosis will gradually develop in many CD patients and results in irreversible fibrosis stricture, causing refractory abdominal pain and even intestinal obstruction, and necessitating one or more surgical interventions. Thus far the exact etiology of CD remains unknown. It is believed that genetic, environmental and immunologic factors are involved, which may also predict the development of intestinal fibrosis. Recent studies have found the association of mutations in genes, such as NOD2, ATG16L1, CX3CR1, IL-23R and MMP3 with the fibrogenic phenotype of CD. In addition, serum extracellular matrix molecules, growth factors, miRNAs and microbial antibodies have also been linked to the fibrogenesis in CD patients, however the results of researches were divergent. Therefore it is of significance to explore noninvasive markers of intestinal fibrosis with high sensitivity and specificity, and the high-throughput proteomic technique may be an approach that deserves further investigation. Screening the high-risk patients for the fibrostenotic phenotype of CD by susceptibility genes, and early detection of intestinal fibrosis using noninvasive serum markers, will help improve the treatment outcomes and reduce the surgical rates. The article aims at summarizing the current susceptibility genes and serum markers of intestinal fibrosis in CD.
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PMID:[Susceptibility genes and serum markers of intestinal fibrosis in Crohn disease]. 2917 4