INTRACEREBROVENTRICULAR INJECTION OF PROSTAGLANDIN E(2) INDUCES THERMAL HYPERALGESIA IN RATS - THE POSSIBLE INVOLVEMENT OF EP(3) RECEPTORS

To determine what types of prostanoid receptors are involved in the central effect of prostaglandin E(2) (PGE(2)) on nociception, we administered PGE(2) and its agonists, i.e., 17-phenyl-omega-trinor PGE(2) (an EP(1) receptor agonist), butaprost (an EP(2) receptor agonist), 11-deoxy PGE(1) (an EP(2)/EP(3) receptor agonist, EP(2) much greater than EP(3)) and M&B28767 (an EP(3) receptor agonist) into the lateral cerebroventricle (LCV) of rats and observed the changes of paw-withdrawal latency on a hot plate. The LCV injection of PGE, (10 pg/kg-l0 ng/kg), Il-deoxy PGE(1) (100 pg/kg-l0 ng/kg) and M&B28767 (I pg/kg-100 pg/kg) produced a significant reduction in the paw-withdrawal latency. The maximal reduction was observed 15 min after the LCV injection of these drugs. Neither 17-phenyl-omega-trinor PGE(2) (1 pg/kg(-1) mu g/kg) nor butaprost (1 pg/kg-100 mu g/kg) induced any significant changes in the paw-withdrawal latency. The LCV injection of PGE(2) (1 mu g/kg) and 17-phenyl-omega-trinor PGE, (50 mu g/kg) increased the latency only 5 min after LCV injection. These findings indicate that the LCV injection of PGE(2) induces thermal hyperalgesia through EP(3) receptors and analgesia through EP(1) receptors by its central action in rats.