Antinociceptive effects of dynorphin peptides in a model of inflammatory pain

Abstract

Dynorphin A (DYN) peptides, administered into the central nervous system, have produced inconsistent analgesic actions in tests using thermal stimuli. This study examined antinociceptive effects of intravenous and intraplantar DYN-(2-17) against noxious pressure in rats with Freund's adjuvant-induced unilateral hindpaw inflammation. The effects of DYN-(2-17) were compared to those of the opioid agonists morphine, ( d-Ala 2, N-Methyl-Phe 4,Gly-ol 5)-enkephalin (DAMGO) and DYN-(1-17). Intravenous DYN-(2-17) (0.188–10 mg/kg) produced dose-dependent elevations of paw pressure thresholds in inflamed and in non-inflamed paws. These effects were similar in magnitude to those of subcutaneous morphine (2 mg/kg), at doses of 0.375–1.5 mg/kg they were significantly greater on the inflamed (right) than on the non-inflamed (left) paw, and they were not reversible by intravenous naloxone (1–10 mg/kg). Intraplantar Dyn-(2-17) (0.001–0.3 mg) was ineffective, whereas both intraplantar DYN-(1-17) (0.15–0.3 mg) and DAMGO (0.008–0.016 mg) produced dose-dependent and naloxone-reversible elevations of paw pressure thresholds. The intraplantar injection of both Dyn peptides produced a transient increase in the volume of non-inflamed paws. These findings suggest that intravenous DYN-(2-17) produces possibly centrally mediated, non-opioid antinociceptive effects against noxious pressure. At certain doses these effects are more potent in inflamed than in non-inflamed paws. In contrast to the opioid peptides DYN-(1-17) and DAMGO, DYN-(2-17) has no peripheral antinociceptive actions.