Open AccessConsequences of altered eicosanoid patterns for nociceptive processing in mPGES‐1‐deficient mice
Author(s) -
Brenneis Christian,
Coste Ovidiu,
Schmidt Ronald,
Angioni Carlo,
Popp Laura,
Nusing Rolf M.,
Becker Wiebke,
Scholich Klaus,
Geisslinger Gerd
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2007.00110.x
Subject(s) - nociception , hyperalgesia , cyclooxygenase , eicosanoid , prostaglandin , prostaglandin e , spinal cord , chemistry , zymosan , endocrinology , medicine , pharmacology , neuroscience , biology , enzyme , biochemistry , arachidonic acid , receptor , in vitro
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 noci‐ceptive 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 2α and 6‐keto‐PGF 1α (stable metabolite of PGI 2 ). Since the latter prostaglandins serve also as mediators of noci‐ception they may compensate the loss of PGE 2 synthesis in mPGES‐1‐deficient mice.