TY - JOUR
T1 - Prostaglandin E receptor EP3 subtype is involved in thermal hyperalgesia through its actions in the preoptic hypothalamus and the diagonal band of Broca in rats
AU - Hosoi, M.
AU - Oka, T.
AU - Hori, T.
N1 - Funding Information:
This research was supported in part by Grant-in-Aids for Scientific Research (No. 06454153 and 06557006 to T. Hori) from the Ministry of Education, Science and Culture, Japan, grant from the Naito Foundation (No. 95–185 to T. Oka) and the grant from the Ichiro Kanehara Foundation (to M. Hosoi). This study was reviewed by the Committee of Ethics on Animal Experiments in the Faculty of Medicine, Kyushu University and was carried out under the control of the Guidelines for Animal Experiments in the Faculty of Medicine, Kyushu University and Law (No. 105) and Notification (No. 6) of the Government.
PY - 1997
Y1 - 1997
N2 - The effects of microinjection of prostaglandin E2 (PGE2) (0.5 fg-500 pg/0.2 μl) 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-ω-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist) and M and B28767 (an EP3 receptor agonist) into the MPO and observed the nociceptive behavior. The intraMPO injection of M and 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 0.055 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 and 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 and 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.
AB - The effects of microinjection of prostaglandin E2 (PGE2) (0.5 fg-500 pg/0.2 μl) 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-ω-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist) and M and B28767 (an EP3 receptor agonist) into the MPO and observed the nociceptive behavior. The intraMPO injection of M and 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 0.055 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 and 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 and 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.
UR - http://www.scopus.com/inward/record.url?scp=0030743541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030743541&partnerID=8YFLogxK
U2 - 10.1016/S0304-3959(97)03380-0
DO - 10.1016/S0304-3959(97)03380-0
M3 - Article
C2 - 9231874
AN - SCOPUS:0030743541
VL - 71
SP - 303
EP - 311
JO - Pain
JF - Pain
SN - 0304-3959
IS - 3
ER -