Linked Life Data

21514055

Source:http://linkedlifedata.com/resource/pubmed/id/21514055

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-13
pubmed:abstractText
Epinephrine (EPI) contributes to hyperalgesia in inflammatory and stress conditions. EPI signals via adrenoceptors, which are regulated by G protein-coupled receptor kinase 2 (GRK2). We previously reported that GRK2 is decreased in nociceptors during chronic inflammation. Herein, we investigated whether GRK2 modulates EPI-induced mechanical and thermal hyperalgesia by using GRK2(+/-) mice, which express 50% of the GRK2 protein. We demonstrate for the first time that EPI-induced mechanical as well as thermal hyperalgesia is prolonged to approximately 21 days in GRK2(+/-) mice, whereas it lasts only 3 to 4 days in wild-type mice. Using cell- specific GRK2-deficient mice, we further show that a low level of GRK2 in primary sensory neurons is critical for this prolongation of EPI-induced hyperalgesia. Low GRK2 in microglia had only a small effect on EPI-induced hyperalgesia. Low GRK2 in astrocytes did not alter EPI-induced hyperalgesia. EPI-induced hyperalgesia was prolonged similarly in mice with tamoxifen-induced homozygous or heterozygous deletion of GRK2. In terms of EPI signalling pathways, the protein kinase A (PKA) inhibitor H-89 inhibited EPI-induced mechanical hyperalgesia in wild-type mice, whereas H-89 had no effect in mice with low GRK2 in sensory neurons (SNS-GRK2(+/-) mice). Conversely, intraplantar injection of the protein kinase C? PKC? inhibitor TAT-PKC(?v1-2) inhibited hyperalgesia in sensory neuron specific (SNS)-GRK2(+/-) mice and not in wild-type mice. These results indicate that low GRK2 in primary sensory neurons switches EPI-induced signalling from a protein kinase A-dependent toward a PKC?-dependent pathway that ultimately mediates prolonged EPI-induced hyperalgesia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1872-6623
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1649-58
pubmed:meshHeading
pubmed-meshheading:21514055-Adrenergic alpha-Antagonists, pubmed-meshheading:21514055-Adrenergic beta-Antagonists, pubmed-meshheading:21514055-Animals, pubmed-meshheading:21514055-Disease Models, Animal, pubmed-meshheading:21514055-Enzyme Inhibitors, pubmed-meshheading:21514055-Epinephrine, pubmed-meshheading:21514055-Female, pubmed-meshheading:21514055-G-Protein-Coupled Receptor Kinase 2, pubmed-meshheading:21514055-Ganglia, Spinal, pubmed-meshheading:21514055-Gene Expression Regulation, pubmed-meshheading:21514055-Hyperalgesia, pubmed-meshheading:21514055-Male, pubmed-meshheading:21514055-Mice, pubmed-meshheading:21514055-Mice, Inbred C57BL, pubmed-meshheading:21514055-Mice, Knockout, pubmed-meshheading:21514055-Neuroglia, pubmed-meshheading:21514055-Pain Measurement, pubmed-meshheading:21514055-Pain Threshold, pubmed-meshheading:21514055-Phentolamine, pubmed-meshheading:21514055-Propanolamines, pubmed-meshheading:21514055-Sensory Receptor Cells, pubmed-meshheading:21514055-Signal Transduction
pubmed:year
2011
pubmed:articleTitle
GRK2 in sensory neurons regulates epinephrine-induced signalling and duration of mechanical hyperalgesia.
pubmed:affiliation
Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
pubmed:publicationType
Journal Article