Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice.
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.
Brenneis
Christian
C
Pharmazentrum Frankfurt, ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Theodor-Stern-Kai 7, Frankfurt, Germany.
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
D000818:Animals; D001522:Behavior, Animal; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D051545:Cyclooxygenase 1 / Q000172:deficiency* / Q000235:genetics; D015777:Eicosanoids / Q000378:metabolism*; D005260:Female; D006930:Hyperalgesia / Q000235:genetics; D007150:Immunohistochemistry; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010147:Pain Measurement; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism
D003470:Culture Media; D015777:Eicosanoids; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse