Antinociceptive effects of dynorphin peptides in a model of inflammatory pain.
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-Ala2,N-Methyl-Phe4,Gly-ol5)-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) does not appear to have no peripheral antinociceptive actions.
Beyer
A
A
Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Schäfer
M
M
Stein
C
C
D000700:Analgesics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D004399:Dynorphins / Q000009:adverse effects / Q000627:therapeutic use*; D004487:Edema / Q000139:chemically induced; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000627:therapeutic use; D005528:Foot; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D000701:Analgesics, Opioid; D004745:Enkephalins; D010446:Peptide Fragments; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004399:Dynorphins; C082245:dynorphin (2-17)