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.