Hyperalgesic action in rats of intracerebroventricularly administered arachidonic acid, PG E2 and PG F2 alpha: effects of analgesic drugs on hyperalgesia.
Hyperalgesic actions in rats of intracerebroventricularly (i.c.v.) administered arachidonic acid, prostaglandin (PG) E2 and PG F2 alpha were studied. For the analgesic assay, vocalization induced by repetitive electrical stimulation was employed. Administered i.c.v., arachidonic acid (0.1-30 micrograms/rat), PG E2 (0.001-0.3 micrograms/rat) and PG F2 alpha (0.01-3 micrograms/rat) potentiated the vocalization, in a dose-dependent manner. The maximal potentiating doses of arachidonic acid, PG E2 and PG F2 alpha were 10 micrograms/rat, 0.1 microgram/rat and 1 microgram/rat, respectively. Indomethacin and diclofenac produced much more potent analgesic effects in arachidonic acid-induced hyperalgesic rats than in normal rats and in PG E2- and PG F2 alpha-induced hyperalgesic rats, but aminopyrine, acetaminophen and morphine produced the same analgesic effect in both hyperalgesic and normal rats. Linoleic acid, linolenic acid and gamma-linolenic acid also induced a weak hyperalgesia, whereas indomethacin (4 mg/kg) failed to attenuate the vocalization in these unsaturated fatty acids-induced hyperalgesic rats. These findings indicate that the hyperalgesic actions of arachidonic acid and its metabolites are related to mediation or modulation of the central pain pathways, and the pain-relieving properties of acidic nonsteroidal antiinflammatory drugs (NSAIDs) may be, at least in part, involved in central site.
Okuyama
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S
Aihara
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H
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008042:Linolenic Acids / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000139:chemically induced*; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology*; D011460:Prostaglandins F / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D017962:alpha-Linolenic Acid; D017965:gamma-Linolenic Acid
D000700:Analgesics; D001095:Arachidonic Acids; D008041:Linoleic Acids; D008042:Linolenic Acids; D011458:Prostaglandins E; D011460:Prostaglandins F; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D017965:gamma-Linolenic Acid; D019787:Linoleic Acid; D015237:Dinoprost; D015232:Dinoprostone