PROSTAGLANDINS: ANTINOCICEPTIVE EFFECT OF PROSTAGLANDIN E1 IN THE RAT

1. The antinociceptive effect of prostaglandins E₁, E₂ and F_2α 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 F_2α (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.