Prostaglandin E2 Receptor Ep4 Contributes to Inflammatory Pain Hypersensitivity.
From: Department of Anesthesiology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chung Gang University, Taiwan, Republic of China.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Dec 2006
- ISSN: 0022-3565
- Volume: 319
- Issue: 3
- Pages: 1096-103
- Medium: Print
- Language: English
- Citation (JAMA): Lin Chung-Ren, Amaya Fumimasa, Barrett Lee, et al. Prostaglandin E2 Receptor Ep4 Contributes to Inflammatory Pain Hypersensitivity.. J. Pharmacol. Exp. Ther. Dec 2006;319:1096-103
Abstract
Prostaglandin E(2) (PGE(2)) is both an inflammatory mediator released at the site of tissue inflammation and a neuromodulator that alters neuronal excitability and synaptic processing. The effects of PGE(2) are mediated by four G-protein-coupled EP receptors (EP1-EP4). Here we show that the EP4 receptor subtype is expressed by a subset of primary sensory dorsal root ganglion (DRG) neurons, and that its levels, but not that of the other EP1-3 subtypes, increase in the DRG after complete Freund’ adjuvant-induced peripheral inflammation. Administration of both an EP4 antagonist [AH23848, (4Z)-7-[(rel-1S,2S,5R)-5-((1,1’-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid] and EP4 knockdown with intrathecally delivered short hairpin RNA attenuates inflammation-induced thermal and mechanical behavioral hypersensitivity, without changing basal pain sensitivity. AH23848 also reduces the PGE(2)-mediated sensitization of capsaicin-evoked currents in DRG neurons in vitro. These data suggest that EP4 is a potential target for the pharmacological treatment of inflammatory pain.
Mesh Headings (Keywords): Animals, Biphenyl Compounds, Blotting, Western, Capsaicin, Cells, Cultured, Dinoprostone, Electrophysiology, Ganglia, Spinal, Heat, Hyperalgesia, Image Processing, Computer-Assisted, Immunohistochemistry, In Situ Hybridization, Inflammation, Injections, Spinal, Male, Neurons, Physical Stimulation, RNA, Small Interfering, Rats, Rats, Sprague-Dawley, Receptors, Prostaglandin E
Check for Full Text / PubMed Unique Identifier (PMID): 16966471
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