The intraspinal release of prostaglandin E2 in a model of acute arthritis is accompanied by an up-regulation of cyclo-oxygenase-2 in the spinal cord.
In anaesthetized rats, the intraspinal release of immunoreactive prostaglandin E2 was measured using antibody microprobes. We addressed the question of whether the release of immunoreactive prostaglandin E2 is altered during development of acute inflammation in the knee evoked by intra-articular injections of kaolin and carrageenan. We also examined cyclo-oxygenase-1 and cyclo-oxygenase-2 protein levels in the spinal cord during the development of inflammation using the same model of arthritis. Densitometric analysis of microprobes showed that basal release of immunoreactive prostaglandin E2 in the period 175-310 min after kaolin was slightly higher than in the absence of inflammation. A pronounced enhancement of basal release of immunoreactive prostaglandin E2 was observed 430-530 min after kaolin. Enhanced levels of immunoreactive prostaglandin E2 were observed throughout the dorsal and ventral horns. Release of immunoreactive prostaglandin E2 was not altered further by the application of innocuous and noxious pressure onto the inflamed knee. Western blot analysis revealed that cyclo-oxygenase-2 but not cyclo-oxygenase-1 protein levels were elevated in the spinal cords of animals with inflammation compared to normal animals. This effect was evident as early as 3 h after the induction of arthritis. The maximum elevation of cyclo-oxygenase-2 protein levels (six-fold) was observed 12 h after the induction of arthritis. The results show that there is a tonic release of immunoreactive prostaglandin E2 from the spinal cord following the induction of arthritis, which is accompanied by enhanced expression of cyclo-oxygenase-2 protein in the spinal cord. We suggest that intraspinal prostaglandins may play a role in inflammation-evoked central sensitization of spinal cord neurons.
Ebersberger
A
A
Physiologisches Institut der Universität Würzburg, Germany.
Grubb
B D
BD
Willingale
H L
HL
Gardiner
N J
NJ
Nebe
J
J
Schaible
H G
HG
D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007616:Kaolin; D008297:Male; D008565:Membrane Proteins; D010146:Pain / Q000235:genetics / Q000378:metabolism; D010812:Physical Stimulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*
D007527:Isoenzymes; D008565:Membrane Proteins; D007616:Kaolin; D012710:Serum Albumin, Bovine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone