1997 Fiscal Year Final Research Report Summary
Role of Cyclooxygenase in the Nociceptive Transmission in the Spinal Cord
| Project/Area Number |
08671715
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Chiba University |
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Principal Investigator |
YAMAMOTO Tatsuo Chiba University, Dept Anesthesiology, Lecturer, 医学部・付属病院, 講師 (20200818)
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| Project Period (FY) |
1996 – 1997
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| Keywords | cyclooxygenase / spinal cord / formalin test / carageenan test / inflammation |
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| Research Abstract |
It has been reported that prostaglandins act as an important modulator of the spinal nociceptive transmission. Cyclooxygenase (COX) is an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. Recently, two different COX forms have been characterized : COX-1 is constitutively expressed and COX-2 is highly inducible in response to inflammatory stimuli. In the normal brain, the level of COX-2 mRNA is substantial. In this project, I investigated the role of COX-2 in the nociceptive transmission in the rat spinal cord by intrathecal injection of NS398, a COX-2 selective inhibitor.
Two inflammatory pain models were used for the analysis of role of COX-2 in the nociceptive transmission in the spinal cord, formalin test and carageenan test. Intrathecal injection of NS398 depressed the agitation behavior induced by paw formalin injection in a dose-dependent manner when NS398 was injected 10 min before the formalin injection. When NS398 was injected 7 min after the formalin injection, NS398 had no effect on the formalin induced agitation behavior. In the carageenan test, two hours after the paw carageenan injection, maximum thermal hyperalgesia was induced. NS398 was injected intrathecally two hours after the carageenan injection. NS398 attenuated the level of thermal hyperalgesia induced by carageenan injection in a dose dependent manner.
These data demonstrated that spinal COX-2 plays an important role in spinal nociceptive transmission during the rat formalin test and carageenan test. These data suggested a promising new therapeutic approach to treating pain during inflammation.
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[Publications] Yamamoto, T.and Nozaki-Taguchi, N.: Analysis of the roles of cyclooxygenase (COX) -1 and COX-2 in spinal nociceptive transmission using indomethacin, a nonselective COX inhibitor, and NS398, a COX-2 selective inhibitor. In : Proceedings of the 8th World Congress on Pain, Progress in Pain Research and Management, Vol. 8, ed T.S.Jensen, J.A.Turner and Z.Wiesenfeld-Hallin, Seattle. IASP Press, 303-312 (1997)
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