We investigated the relationship between c-fos expression in the hind brain and peritoneal prostaglandin (PG) synthesis after visceronociceptive stimulation with acetic acid in rats. Time-course studies on the mRNA expression for c-fos in the hind brain and cyclooxygenase (COX) isoforms in the peritoneal cells, as well as on the peritoneal 6-keto-PGF 1 α accumulation, after stimulation indicated that COX-1 but not COX-2 was responsible for the peritoneal synthesis of PGs which were suggested to evoke c-fos expression in the hind brain. Pharmacological experiments using mofezolac, a preferential inhibitor against COX-1, and NS-398, a selective inhibitor against COX-2, confirmed the involvement of COX-1 derived PGs in the induction of c-fos expression in the hind brain following the noxious stimulation.