Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice

  • Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E2 synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2 synthase-1 (mPGES-1) isomerizes COX-2-derived PGH2 to PGE2. Here, we evaluated the effect of mPGES-1-deficiency on the noci-ceptive behavior in various models of nociception that depend on PGE2 synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES-1-deficient mice despite a marked decrease of the spinal PGE2 synthesis. Similarly, the nociceptive behavior was unaltered in mPGES-1-deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES-1-deficient mice showed a redirection of the PGE2 synthesis to PGD2, PGF2α and 6-keto-PGF1α (stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci-ception they may compensate the loss of PGE2 synthesis in mPGES-1-deficient mice.

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Author:Christian Brenneis, Ovidiu Coste, Ronald Schmidt, Carlo Federico Angioni, Laura Popp, Rolf M. Nusing, Wiebke Becker, Klaus Scholich, Gerd GeisslingerORCiDGND
Pubmed Id:
Parent Title (English):Journal of cellular and molecular medicine
Place of publication:Hoboken, NJ
Document Type:Article
Date of Publication (online):2007/08/31
Date of first Publication:2007/08/31
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/02/08
Tag:cyclooxygenase; hyperalgesia; mPGES-1; pain; prostaglandin; spinal cord
Page Number:10
First Page:639
Last Page:648
©2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Medizin / Medizin
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0