Induction, blockade and restoration of a persistent hypersensitive state.
A new model of chronic hypersensitivity was developed in the rat by daily intraplantar administration of either prostaglandin E2 dopamine or isoprenaline, for a period of 2 weeks. Like other hyperalgesic mediators, dibutyryl-cAMP, when applied to the paws, caused an acute effect but did not produce persistent hypersensitivity. The persistent hypersensitive state was not affected by a typical non-steroidal anti-inflammatory drug (indomethacin), was temporarily inhibited by a centrally acting analgesic (morphine), was partially inhibited by a protein synthesis inhibitor (cycloheximide) and abolished by a single dose of peripherally acting analgesics such as dipyrone or N-methyl morphine. Once the residual hypersensitivity had been abolished with dipyrone or N-methyl morphine, a small dose of prostaglandin E2, dopamine or Interleukin-1 beta, which in normal animals causes a mild and short lived effect, restored the persistent hypersensitive state. This ability to restore the persistent effect was not observed with intraplantar administration of dibutyryl-cAMP. Our results suggest the existence of a peripheral trace of inflammatory pain, a phenomenon which may be associated with stimulation of neuronal adenylate cyclase and protein synthesis. This concept may explain part of the puzzle of chronic inflammatory pain and lead to the development of new analgesics.
Ferreira
Sergio H
SH
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, 14049 Ribeirão Preto, S.P.Brazil.
Lorenzetti
Berenice B
BB
De Campos
Dangelo I
DI
D000818:Animals; D003994:Bucladesine; D002908:Chronic Disease; D004177:Dipyrone / Q000494:pharmacology; D004298:Dopamine; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D011458:Prostaglandins E; D051381:Rats; D011919:Rats, Inbred Strains
D011458:Prostaglandins E; D003994:Bucladesine; D004177:Dipyrone; D004298:Dopamine