m&b-28-767 and Pain

The effects of microinjection of prostaglandin E2 (PGE2) (0.5 fg-500 pg/0.2 microl) into the medial part of the preoptic area (MPO) on nociception were studied using a hot-plate test in rats. The intraMPO microinjection of PGE2 only at non-pyrogenic doses (5-50 fg) reduced the paw-withdrawal latency, suggesting hyperalgesia. Maximal reduction was obtained 15 min after the injection of PGE2 at 50 fg. Subsequently, to determine which types of prostanoid receptors are involved in the hyperalgesic effect of PGE2 in the MPO, we administered PGE2 receptor agonists, i.e., 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist) and M&B28767 (an EP3 receptor agonist) into the MPO and observed the nociceptive behavior. The intraMPO injection of M&B28767 (0.005 fg-50 pg), like that of PGE2, exhibited a U-shaped dose response characteristic, i.e., a significant decrease of the paw-withdrawal latency only at 0.05-5 fg with the maximal response at 0.5 fg. However, neither the administration of EP1 (0.5 fg-50 ng) nor EP2 (0.5 fg-500 pg) agonists had any effect on nociception. The microinjection of M&B28767 at 0.5 fg into the other parts of preoptic hypothalamus (the lateral part of the preoptic area and the median preoptic nucleus) and the diagonal band of Broca (DBB) produced hyperalgesia similar to the intraMPO-induced hyperalgesia in terms of magnitude and time course. Microinjection of M&B28767 (0.5 fg) into either the paraventricular nucleus, the ventromedial hypothalamus, the lateral hypothalamic area or the septal nucleus had no effect on nociception. These findings suggest that PGE2 at non-pyrogenic doses in the brain induces hyperalgesia, at least in part, through its actions on EP3 receptors in the preoptic hypothalamus and the DBB in rats.

Topics: Alprostadil; Analysis of Variance; Animals; Brain Mapping; Frontal Lobe; Hot Temperature; Hyperalgesia; Male; Microinjections; Pain; Preoptic Area; Prosencephalon; Rats; Rats, Wistar; Receptors, Prostaglandin E

To determine what types of prostanoid receptors are involved in the central effect of prostaglandin E2 (PGE2) on nociception, we administered PGE2 and its agonists, i.e., 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist), 11-deoxy PGE1 (an EP2/EP3 receptor agonist, EP2 >> EP3) and M&B28767 (an EP3 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 PGE2 (10 pg/kg-10 ng/kg), 11-deoxy PGE1 (100 pg/kg-10 ng/kg) and M&B28767 (1 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 PGE2 (1 pg/kg-1 microgram/kg) nor butaprost (1 pg/kg-100 microgram/kg) induced any significant changes in the paw-withdrawal latency. The LCV injection of PGE2 (1 microgram/kg) and 17-phenyl-omega-trinor PGE2 (50 micrograms/kg) increased the latency only 5 min after LCV injection. These findings indicate that the LCV injection of PGE2 induces thermal hyperalgesia through EP3 receptors and analgesia through EP1 receptors by its central action in rats.

Topics: Alprostadil; Animals; Dinoprostone; Hot Temperature; Hyperalgesia; Injections, Intraventricular; Male; Pain; Prostaglandins E, Synthetic; Rats; Rats, Wistar; Receptors, Prostaglandin E