Prostaglandins: antinociceptive effect of prostaglandin E1 in the rat.

1. The antinociceptive effect of prostaglandins E1, E2 and F2alpha was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E1 (PGE1) produced a dose-related antinociceptive activity. 2. The antinociceptive activities of equi-analgesic doses of morphine (7.5. mg/kg, i.p.) and PGE1 (2.0 mg/kg, i.p.) were inhibited to almost similar extents after pretreatment with drugs known to reduce central turnover of serotonin receptors, namely reserpine, fenclonine (p-chlorophenylalanine), methysergide and 5,6-dihydroxytryptamine. 3. Prostaglandin F2alpha (2.0 mg/kg, i.p.) significantly inhibited the antinociceptive effects of both morphine and PGE1. 4. The prostaglandin synthesis inhibitors, indomethacin and diclofenac, significantly inhibited morphine analgesia. 5. Probenecid markedly prolonged the duration of antinociceptive effect of morphine and the duration of PGE1-induced potentiation of subanalgesic dose of morphine. 6. The results suggest that, in albino rats, PGE1-induced antinociceptive activity is serotonin mediated and that morphine analgesia is not only mediated through serotonin but also through prostaglandins (PGE1 ?) and 5-hydroxyindole acetic acid, the serotonin metabolite.