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The Journal of Neuroscience, September 28, 2005, 25(39):9005-9009; doi:10.1523/JNEUROSCI.2190-05.2005

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BRIEF COMMUNICATION
Downregulation of Cytosolic Prostaglandin E2 Synthase Results in Decreased Nociceptive Behavior in Rats

Annette Hofacker, Ovidiu Coste, Hong-Van Nguyen, Claudiu Marian, Klaus Scholich, and Gerd Geisslinger

Pharmazentrum Frankfurt, Zentrum für Arzneimittelforschung, Entwicklung, und Sicherheit, Klinikum der Johann Wolfgang Goethe–Universität Frankfurt, 60590 Frankfurt, Germany

Nociception-evoked prostaglandin E2 (PGE2) release in the spinal cord contributes considerably to the development of hyperalgesia and allodynia. Biosynthesis of PGE2 involves the conversion of arachidonic acid to PGH2 by cyclooxygenases (COXs), followed by an isomerization of PGH2 to PGE2 by PGE2 synthases (PGESs). The roles of COX-1, COX-2, and the inducible microsomal PGES-1 have been studied in models of pain and inflammation. In contrast, in nociceptive processes, very little is known about the role of cytosolic PGES (cPGES), which has been described as being functionally coupled to COX-1. Here we show by in situ hybridization and immunohistological analysis that COX-1 and cPGES are constitutively expressed in neuronal and non-neuronal cells of the dorsal and ventral horns in the spinal cord of adult rats. The protein levels of both enzymes were not regulated by nociceptive stimuli; however, reduction of cPGES in rat spinal cord with intrathecal application of cPGES antisense oligonucleotides reduced the nociceptive behavior in zymosan-evoked thermal hyperalgesia and in the formalin assay. The data indicate that cPGES plays an important role in mediating early responses during spinal nociceptive processing.

Key words: pain; spinal cord; nociception; prostaglandin; prostaglandin synthase; hyperalgesia


Received May 31, 2005; revised July 21, 2005; accepted July 21, 2005.




This article has been cited by other articles:


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AM J ALZHEIMERS DIS OTHER DEMENHome page
U. A. Chaudhry and S. Dore
Cytosolic Prostaglandin E Synthase: Expression Patterns in Control and Alzheimer's Disease Brains
American Journal of Alzheimer's Disease and Other Dementias, February 1, 2009; 24(1): 46 - 51.
[Abstract] [PDF]


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J. Biol. Chem.Home page
O. Coste, C. Brenneis, B. Linke, S. Pierre, C. Maeurer, W. Becker, H. Schmidt, W. Gao, G. Geisslinger, and K. Scholich
Sphingosine 1-Phosphate Modulates Spinal Nociceptive Processing
J. Biol. Chem., November 21, 2008; 283(47): 32442 - 32451.
[Abstract] [Full Text] [PDF]



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