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

ABSTRACT: Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E(2) synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE(2) synthase-1 (mPGES-1) isomerizes COX-2-derived PGH(2) to PGE(2). Here, we evaluated the effect of mPGES-1-deficiency on the nociceptive behavior in various models of nociception that depend on PGE(2) 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 PGE(2) 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 PGE(2) synthesis to PGD(2), PGF(2alpha) and 6-keto-PGF(1alpha) (stable metabolite of PGI(2)). Since the latter prostaglandins serve also as mediators of nociception they may compensate the loss of PGE(2) synthesis in mPGES-1-deficient mice.

SUBMITTER: Brenneis C

PROVIDER: S-EPMC3822549 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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

Brenneis Christian C Coste Ovidiu O Schmidt Ronald R Angioni Carlo C Popp Laura L Nusing Rolf M RM Becker Wiebke W Scholich Klaus K Geisslinger Gerd G

Journal of cellular and molecular medicine 20080401 2

Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E(2) synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE(2) synthase-1 (mPGES-1) isomerizes COX-2-derived PGH(2) to PGE(2). Here, we evaluated the effect of mPGES-1-deficiency on the nociceptive behavior in various models of nociception that depend on PGE(2) synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was n ...[more]

PMID: 18419601

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

Publications

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

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