Dynorphin-(1-8) inhibits the release of substance P-like immunoreactivity in the spinal cord of rats following a noxious mechanical stimulus.
This study was conducted to determine the effect of the opioid peptide dynorphin-(1-8) on the release of substance P-like immunoreactivity in the dorsal horn during mechanical activation of peripheral nociceptors. A push-pull cannula was used to perfuse the dorsal horn of decerebrate/spinal transected rats before, during and following the application of a noxious mechanical stimulus to the ipsilateral hindpaw and lower limb. The collected perfusates were assayed for substance P-like immunoreactivity using radioimmunoassay. Dynorphin-(1-8) applied to the spinal cord at a concentration of 1 microM reduced the basal release of substance P-like immunoreactivity by 28 +/- 11% and prevented the mechanically evoked release of substance P-like immunoreactivity. This effect of dynorphin-(1-8) was reversed by 2 microM of the selective kappa-opioid receptor antagonist nor-binaltorphimine. Moreover, blockade of the kappa-opioid receptors by nor-binaltorphimine resulted in a 33 +/- 5% increase in the basal release of substance P-like immunoreactivity. These data show that activation of nor-binaltorphimine-sensitive sites by dynorphin-(1-8) results in inhibition of the release of substance P-like immunoreactivity in the dorsal horn of the rat.
Zachariou
V
V
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-7605, USA.
Goldstein
B D
BD
D000818:Animals; D003655:Decerebrate State; D004399:Dynorphins / Q000494:pharmacology*; D006614:Hindlimb; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010812:Physical Stimulation; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000037:antagonists & inhibitors*
D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; D013373:Substance P; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; C026770:dynorphin (1-8)