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Cyclooxygenase‐2 is induced in the endothelial cells throughout the central nervous system during carrageenan‐induced hind paw inflammation; its possible role in hyperalgesia
Author(s) -
Ibuki Takae,
Matsumura Kiyoshi,
Yamazaki Yasuo,
Nozaki Taiki,
Tanaka Yoshifumi,
Kobayashi Shigeo
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01848.x
Subject(s) - hyperalgesia , carrageenan , inflammation , cyclooxygenase , prostaglandin , pharmacology , central nervous system , prostaglandin e2 , eicosanoid , medicine , chemistry , endocrinology , immunology , nociception , biochemistry , receptor , enzyme , arachidonic acid
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 E 2 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.