Antinociceptive effects of mu- and kappa-agonists in inflammation are enhanced by a peripheral opioid receptor-specific mechanism

Eur J Pharmacol. 1988 Oct 18;155(3):255-64. doi: 10.1016/0014-2999(88)90511-0.


Rats received an injection of Freund's complete adjuvant into the right hindpaw and developed localized inflammation. Four to six days after inoculation, the antinociceptive effect of both the mu-agonist, morphine, and the kappa-agonist U-50,488H, administered subcutaneously, was markedly enhanced in the inflamed paws. This effect was dose dependently antagonized by low dose of intraplantar, but not subcutaneous or intravenous, (-)-naloxone. (+)-Naloxone was inactive. These data indicate that the enhanced antinociceptive effects of both agonists in inflammation are mediated by a peripheral, opioid receptor-specific mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics*
  • Animals
  • Freund's Adjuvant
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / physiopathology
  • Male
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / physiology
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Stereoisomerism


  • Analgesics
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Naloxone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Morphine
  • Freund's Adjuvant