COMPARISON OF PROSTAGLANDIN E(1)-INDUCED AND PROSTAGLANDIN E(2)-INDUCED HYPERALGESIA IN THE RAT

We have studied prostaglandin E(1)-induced mechanical hyperalgesia in the rat hindpaw, by assessing paw-withdrawal thresholds, before and after injecting prostaglandin E(1) alone or with other agents, in normal and streptozotocin-induced diabetic rats. In normal and diabetic rats, prostaglandin E(1) (1-1000 ng) produced a dose-dependent decrease in mechanical nociceptive threshold. In diabetic rats, prostaglandin E(1) was more potent than in normal rats, in producing hyperalgesia, whereas prostaglandin E(2) hyperalgesia was not changed in normal and diabetic rats. Prostaglandin E(1)-induced hyperalgesia was not inhibited by E-type 1 prostaglandin receptor antagonists, SC19220 or SC51089, either in normal or diabetic rats. In fact, in the presence of SC19220, prostaglandin E(1) produced enhanced hyperalgesia, in normal rats. Prostaglandin E(1) hyperalgesia was not significantly modified by sympathectomy or indomethacin. Unlike prostaglandin E(2), prostaglandin E(1) hyperalgesia was not blocked by the inhibitor of the stimulatory guanine nucleotide-binding regulatory protein, guanosine 5'-O-(2-thiodiphosphate). It is suggested that prostaglandin E(1) decreases primary afferent nociceptive threshold directly, by activating a prostaglandin receptor other than the E-type 1 prostaglandin receptor, and that this receptor is not coupled to a stimulatory guanine nucleotide-binding regulatory protein.