Inhibition of noxious stimulus-induced spinal prostaglandin E-2 release byflurbiprofen enantiomers: A microdialysis study

Citation
G. Geisslinger et al., Inhibition of noxious stimulus-induced spinal prostaglandin E-2 release byflurbiprofen enantiomers: A microdialysis study, J NEUROCHEM, 74(5), 2000, pp. 2094-2100
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
74
Issue
5
Year of publication
2000
Pages
2094 - 2100
Database
ISI
SICI code
0022-3042(200005)74:5<2094:IONSSP>2.0.ZU;2-U
Abstract
Peripheral noxious stimuli have been shown to induce prostaglandin (PG) E-2 release at the site of inflammation and in the spinal cord. The antiinflam matory and antinociceptive effects of cyclooxygenase-inhibiting drugs are t hought to depend on the inhibition of PG synthesis. R-Flurbiprofen, however , does not inhibit cyclooxygenase activity in vitro but still produces anti nociceptive effects. To find out whether R-flurbiprofen acts via inhibition of spinal PG release, concentrations of PGE(2) and flurbiprofen in spinal cord tissue were assessed by microdialysis. The catheter was transversally implanted through the dorsal horns of the spinal cord at level L4. R- and S -flurbiprofen (9 and 27 mg kg(-1), respectively) were administered intraven ously 10-15 min before subcutaneous injection of formalin into the dorsal s urface of one hindpaw. Flurbiprofen was rapidly distributed into the spinal cord with maximal concentrations after 30-45 min. Baseline PGE(2) dialysat e concentrations were 100.6 +/- 6.4 pg ml(-1) (mean +/- SEM). After formali n injection they rose about threefold with a maximum of 299.4 +/- 68.4 pg m l(-1) at 7.5 min. After similar to 1 h PGE(2) levels returned to baseline. Both flurbiprofen enantiomers completely prevented the formalin-induced inc rease of spinal PGE(2) release and reduced PGE(2) concentrations below basa l levels. S- and R-flurbiprofen at 9 mg kg(-1) produced a minimum of 15.8 /- 5.2 and 27.7 +/- 14.9 pg ml(-1), respectively, and 27 mg kg(-1) S- and R -flurbiprofen resulted in 11.7 +/-: 1.7 and 9.3 +/- 4.7 pg ml(-1) respectiv ely. PGE(2) levels remained at the minimum up to the end of the observation period at 5 h. When 27 mg kg(-1) R-flurbiprofen was injected intravenously without subsequent formalin challenge, baseline immunoreactive PGE(2) conc entrations were not affected. S-Flurbiprofen (27 mg kg(-1)), however, led t o a moderate reduction (similar to 40%). The data suggest that antinocicept ion produced by R-flurbiprofen is mediated at least in part by inhibition o f stimulated spinal PGE(2) release and support the current view that increa sed spinal PGE(2) release significantly contributes to nociceptive processi ng.