Major roles of prostanoid receptors IP and EP3 in endotoxin-induced enhancement of pain perception

To know the roles of prostaglandin I (IP) and prostaglandin E (EP) receptors in pain perception, we compared the acetic acid-induced writhing response in mice deficient in prostaglandin receptors, i.e. IP, EP1, EP2, EP3, or EP4, with or without lipopolysaccharide (LPS) pretreatment. Without LPS pretreatment, IP-receptor deficient mice showed a significantly smaller number of responses, as previously reported, whereas mice deficient in any of the EP-receptor subtypes showed a number of writhings similar to those of wild-type mice. When mice were pretreated with LPS for 24 hr to induce cyclooxygenase-2 expression, the wild-type as well as EP1-, EP2-, or EP4-receptor-deficient mice showed a similar enhanced writhing response, whereas IP- and EP3-receptor-deficient mice had a significantly less enhanced number of writhings. Three results indicate that IP and EP, are the major prostaglandin receptors mediating the enhanced acetic acid-induced writhing response in mice pre-exposed to LPS, i.e. in endotoxin-enhanced inflammatory nociception. (C) 2001 Elsevier Science Inc. All rights reserved.