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.