Hyperalgesic action in mice of intracerebroventricularly administered arachidonic acid, PG E2, PG F2 alpha and PG D2: effects of analgesic drugs on hyperalgesia.
Hyperalgesic actions in mice of intracerebroventricularly (i.c.v.) administered arachidonic acid, prostaglandin (PG) E2, PG F2 alpha and PG D2 were studied. For the analgesic assay, the mouse tail pressure method was employed. The i.c.v. administration of arachidonic acid (0.01-100 micrograms/mouse), PG E2 (0.01-100 ng/mouse), PG F2 alpha (0.1-1000 ng/mouse) and PG D2 (0.1-1000 ng/mouse) decreased the pain threshold in a dose dependent manner. The doses that produced the maximal decrease in pain threshold for arachidonic acid, PG E2, PG F2 alpha and PG D2 were 10 micrograms/mouse, 10 ng/mouse, 100 ng/mouse and 100 ng/mouse, respectively. Acidic nonsteroidal antiinflammatory drugs (NSAIDs) produced much more potent analgesic effects in arachidonic acid-induced hyperalgesic mice than in normal mice and in PG E2-, PG F2 alpha- and PG D2-induced hyperalgesic mice, but nonacidic NSAIDs and morphine produced the same analgesic effect in both hyperalgesic and normal mice. Linoleic acid, linolenic acid and gamma-linolenic acid induced weak hyperalgesia, but this unsaturated fatty acids-induced hyperalgesia was not affected by indomethacin (2 mg/kg, p.o.). These findings indicate that the arachidonic acid and its metabolites were related to mediation or modulation of central pain pathways and that the central nervous system may be partially involved in the action of acidic NSAIDs.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D011448:Prostaglandin Antagonists; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D012684:Sensory Thresholds / Q000187:drug effects
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2