A spinal mechanism for the peripheral anti-inflammatory action of indomethacin

被引:26
作者
Daher, JB
Tonussi, CR
机构
[1] Univ Fed Santa Catarina, Dept Pharmacol, BR-88010970 Florianopolis, SC, Brazil
[2] State Univ Ponta Grossa, Dept Pharmaceut Sci, Ponta Grossa, PR, Brazil
关键词
indomethacin; prostaglandin E-2; spinal cord; edema; dorsal root reflex;
D O I
10.1016/S0006-8993(02)04056-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present study, we evaluated the consequences of prostaglandin E-2 (PGE(2)) or indomethacin injection into the spinal cord, on a model of peripheral inflammatory edema. Male Wistar rats (200-250 g) received PGE(2) (10 and 100 ng), intrathecally, at 2, 15, 30, and 60 min before an intraplantar carrageenan (CG; 300 mug) injection into the right hindpaw. The developing edema was measured hourly after CG injection, and the groups injected with PGE(2) 30 and 60 min before CG, presented significant edema potentiation. On the other hand, indomethacin (0.3, 0.6, 1.2, 2.5, and 5.0 mug) given intrathecally 60 min before CG injection, inhibited edema formation dose-dependently. The indomethacin effect was not inhibited by aminoglutethimide, which suggests that it was independent of endogenous steroid production. In addition, intrathecally given PGE(2) (10. and 100 ng) dose-dependently reversed the anti-edematogenic effect of indomethacin given by the same route (2.5 mug, i.t.). This suggests that the anti-edematogenic effect produced by intrathecally given indomethacin is probably due to prostaglandin synthesis inhibition at the spinal cord. It is suggested here that during inflammation, prostaglandin may be released into the spinal cord potentiating dorsal root reflexes that contribute to the peripheral edema formation. The inhibition of this potentiation by indomethacin may be a mechanism embedded into the overall anti-inflammatory action of this drug. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:207 / 212
页数:6
相关论文
共 29 条
[1]   PGI2-INDUCED ACTIVATION AND SENSITIZATION OF ARTICULAR MECHANONOCICEPTORS [J].
BIRRELL, GJ ;
MCQUEEN, DS ;
IGGO, A ;
COLEMAN, RA ;
GRUBB, BD .
NEUROSCIENCE LETTERS, 1991, 124 (01) :5-8
[2]   THE EFFECTS OF CAPSAICIN, BRADYKININ, PGE2 AND CICAPROST ON THE DISCHARGE OF ARTICULAR SENSORY RECEPTORS INVITRO [J].
BIRRELL, GJ ;
MCQUEEN, DS .
BRAIN RESEARCH, 1993, 611 (01) :103-107
[3]   EFFECTS OF BRADYKININ AND PROSTAGLANDIN-E1 ON RAT CUTANEOUS AFFERENT NERVE ACTIVITY [J].
CHAHL, LA ;
IGGO, A .
BRITISH JOURNAL OF PHARMACOLOGY, 1977, 59 (02) :343-347
[4]  
Dirig D. M., 1998, Society for Neuroscience Abstracts, V24, P397
[5]  
Dirig DM, 1998, J PHARMACOL EXP THER, V285, P1031
[6]   Intrathecal administration of prostaglandin E(2) causes sensitization of the primary afferent neuron via the spinal release of glutamate [J].
Ferreira, SH ;
Lorenzetti, BB .
INFLAMMATION RESEARCH, 1996, 45 (10) :499-502
[7]   Role of a Ca2+-dependent slow afterhyperpolarization in prostaglandin E(2)-induced sensitization of cultured rat sensory neurons [J].
Gold, MS ;
Shuster, MJ ;
Levine, JD .
NEUROSCIENCE LETTERS, 1996, 205 (03) :161-164
[8]   Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors [J].
Gold, MS ;
Reichling, DB ;
Shuster, MJ ;
Levine, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (03) :1108-1112
[9]   CAPSAICIN-EVOKED PROSTAGLANDIN E(2) RELEASE IN SPINAL-CORD SLICES - RELATIVE EFFECT OF CYCLOOXYGENASE INHIBITORS [J].
MALMBERG, AB ;
YAKSH, TL .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 271 (2-3) :293-299
[10]  
MALMBERG AB, 1992, J PHARMACOL EXP THER, V263, P136