A spinal mechanism for the peripheral anti-inflammatory action of indomethacin.
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 microg) 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 microg) 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 microg, 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.
Daher
Josélia Borba
JB
Department of Pharmacology, Federal University of Santa Catarina, Campus Universitário-Trindade, Caixa Postal 476, 88.010-970 Florianópolis, SC, Brazil.
Tonussi
Carlos Rogério
CR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006614:Hindlimb; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D015232:Dinoprostone; D007213:Indomethacin