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
URN:urn:nbn:de:hebis:30:3-279223
URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822549/
DOI:https://doi.org/10.1111/j.1582-4934.2007.00110.x
ISSN:1582-4934
ISSN:1582-1838
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/18419601
Parent Title (English):Journal of cellular and molecular medicine
Publisher:Wiley-Blackwell
Place of publication:Hoboken, NJ
Document Type:Article
Language:English
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
Volume:12
Issue:2
Page Number:10
First Page:639
Last Page:648
Note:
©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 http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
HeBIS-PPN:327962402
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
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0