Abstract | BACKGROUND: PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF) is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs) reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha ( TNFalpha) and interleukin-1beta (IL-1beta) expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS:
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Authors | Shigeo Hasegawa, Yuta Kohro, Miho Shiratori, Satoshi Ishii, Takao Shimizu, Makoto Tsuda, Kazuhide Inoue |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 5
Pg. e10467
(May 03 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 20454616
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclooxygenase Inhibitors
- Inflammation Mediators
- Interleukin-1beta
- Lipoxygenase Inhibitors
- Platelet Activating Factor
- Platelet Membrane Glycoproteins
- Receptors, G-Protein-Coupled
- Receptors, Lysophosphatidic Acid
- Tumor Necrosis Factor-alpha
- platelet activating factor receptor
- 1-Acylglycerol-3-Phosphate O-Acyltransferase
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Topics |
- 1-Acylglycerol-3-Phosphate O-Acyltransferase
(metabolism)
- Animals
- Cyclooxygenase Inhibitors
(pharmacology)
- Disease Models, Animal
- Ganglia, Spinal
(drug effects, enzymology, pathology)
- Inflammation Mediators
(metabolism)
- Injections
- Interleukin-1beta
(genetics, metabolism)
- Lipoxygenase Inhibitors
(pharmacology)
- Mice
- Models, Biological
- Pain
(metabolism, pathology)
- Peripheral Nerve Injuries
- Peripheral Nerves
(drug effects, pathology)
- Platelet Activating Factor
(pharmacology)
- Platelet Membrane Glycoproteins
(antagonists & inhibitors, deficiency, genetics, metabolism)
- Rats
- Receptors, G-Protein-Coupled
(antagonists & inhibitors, deficiency, genetics, metabolism)
- Receptors, Lysophosphatidic Acid
(antagonists & inhibitors, metabolism)
- Touch
(drug effects)
- Tumor Necrosis Factor-alpha
(genetics, metabolism)
- Up-Regulation
(drug effects)
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