Antinociceptive profiles of opioid peptide agonists in a rat tooth pulp stimulation procedure

The analgesic activity of the prototypic opioid peptides for the mu (D-Ala 2-Me-Phen 1-Gly-ol 5-enkephalin [DAGO]) kappa (Dynorphin 1–13), delta (D-Ala 2-D-Leu 5-enkephalin [DADLE]), or epsilon (β-endorphin) receptor was assessed in a rat tooth pulp stimulation procedure. All opioid peptides tested and the opioid alkaloid U50, 488H (kappa receptor agonist) significantly elevated response thresholds. The rank order of potency based on the Minimum Effective Dose values was β-endorphin > DAGO = dynorphin A (1–13) amide > DADLE > dynorphin A (1–13) > U50,488H. Based on absolute magnitude, the rank order of dose response slopes was DAGO > U50,488H > dynorphin A (1–13) amide > β-endorphin > DADLE. Dynorphin A (1–13) produced the shallowest dose response slope and the magnitude of response threshold was the lowest for all compounds tested. Finally, the general conclusion that mu agonists are effective against noxious stimuli derived from thermal, chemical, and mechanical is extended by our data to include electrical sources derived from tooth pulp stimulation; kappa agonists are effective against noxious stimuli derived from chemical, mechanical, and electrical sources (tooth pulp stimulation) and delta agonists are effective analgesics against thermal, chemical and electrical stimuli (tooth pulp stimulation).