title: Cyclooxygenase-2 is induced in the endothelial cells throughout the central nervous system during carrageenan-induced hind paw inflammation; its possible role in hyperalgesia.
abstract: Inflammation is often accompanied with hyperalgesia. This hyperalgesia is mediated partly by prostaglandin(s) produced in the CNS through the cyclooxygenase-2 (COX-2) dependent pathway. However, it remains unclear where COX-2 is induced in the CNS during inflammation, and how it is involved in hyperalgesia. We studied the precise site of COX-2 induction in the CNS, the relation between the time course of COX-2 induction and that of hyperalgesia, and the effect of COX-2-selective inhibitor by using a carrageenan model. Carrageenan injection induced expression of COX-2-like immunoreactivity in vascular endothelial cells throughout the CNS. This response became evident by 3 h, and was most prominent at 6 h after carrageenan injection. This COX-2 induction was associated with an elevation of prostaglandin E2 in the cerebrospinal fluid, being evident at 3 h, larger at 6 h, and alleviated by a COX-2-selective inhibitor. Thermal hyperalgesia became evident at 1 h, further increased thereafter, and remained elevated until 6 h. Intrathecal administration of COX-2-selective inhibitor 2 h after the carrageenan injection exerted a prominent therapeutic effect on hyperalgesia. These results demonstrate that, during carrageenan-induced inflammation, endothelial cells are the major source of prostaglandin(s) in the CNS, and this endothelial expression of COX-2 is involved in the inflammation-induced hyperalgesia.
authors.affiliation: Anesthesiology, Graduate School of Medical Science and Radiology, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto, Japan. tibuki@koto.kpu-m.ac.jp
authors.forename: Takae
authors.initials: T
authors.lastname: Ibuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsumura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Taiki
authors.initials: T
authors.lastname: Nozaki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002351:Carrageenan; D002490:Central Nervous System / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010147:Pain Measurement; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D002351:Carrageenan; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone