| http://purl.uniprot.org/citations/20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20609517 | http://www.w3.org/2000/01/rdf-schema#comment | "Chronic pain associated with inflammation is a major clinical problem, but the underlying mechanisms are incompletely understood. Recently, we reported that GRK2(+/-) mice with a approximately 50% reduction of GRK2 develop prolonged hyperalgesia following a single intraplantar injection of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). Here we show that spinal microglia/macrophage GRK2 is reduced during chronic inflammation-induced hyperalgesia. Next, we applied CRE-Lox technology to create mice with low GRK2 in microglia/macrophages/granulocytes (LysM-GRK2(f/+)), or sensory neurons or astrocytes. Only mice deficient in microglial/macrophage/granulocyte GRK2 display prolonged IL-1beta-induced hyperalgesia that lasts up to 8days. Two days after intraplantar IL-1beta, increased microglial/macrophage activity occurs in the lumbar but not thoracic spinal cord of GRK2-deficient mice. Intrathecal pre-treatment with minocycline, an inhibitor of microglia/macrophage activation, accelerates resolution of hyperalgesia independent of genotype and prevents transition to chronic hyperalgesia in GRK2(+/-) mice. Ongoing hyperalgesia in GRK2(+/-) mice is reversed by minocycline administration at days 1 and 2 after IL-1beta injection. Similarly, IL-1beta-induced hyperalgesia in LysM-GRK2(f/+) mice is attenuated by intrathecal administration of anti-CX3CR1 to abrogate fractalkine signaling, the p38 inhibitor SB239063 and the IL-1 antagonist IL-1ra. These data establish that chronic inflammatory hyperalgesia is associated with reduced GRK2 in microglia/macrophages and that low GRK2 in these cells is sufficient to markedly prolong hyperalgesia after a single intraplantar injection of IL-1beta. Ongoing hyperalgesia is maintained by spinal microglial/macrophage activity, fractalkine signaling, p38 activation and IL-1 signaling. We propose that chronic inflammation decreases spinal microglial/macrophage GRK2, which prevents silencing of microglia/macrophage activity and thereby contributes to prolonged hyperalgesia."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.pain.2010.06.015"xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Eijkelkamp N."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Heijnen C.J."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Kavelaars A."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Willemen H.L.D.M."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Dorn G.W."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Dantzer R."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/author | "Kelley K.W."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/name | "Pain"xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/pages | "550-560"xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/title | "Microglial/macrophage GRK2 determines duration of peripheral IL-1beta-induced hyperalgesia: contribution of spinal cord CX3CR1, p38 and IL-1 signaling."xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://purl.uniprot.org/core/volume | "150"xsd:string |
| http://purl.uniprot.org/citations/20609517 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20609517 |
| http://purl.uniprot.org/citations/20609517 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20609517 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JGA8-mappedCitation-20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20609517 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JGH2-mappedCitation-20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20609517 |
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| http://purl.uniprot.org/uniprot/#_A0A0G2JEJ6-mappedCitation-20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20609517 |
| http://purl.uniprot.org/uniprot/#_Q0VBK8-mappedCitation-20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20609517 |
| http://purl.uniprot.org/uniprot/#_A0A0R5RP33-mappedCitation-20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20609517 |
| http://purl.uniprot.org/uniprot/#_A0A0R5RP34-mappedCitation-20609517 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20609517 |