Dynorphin-(1-8) inhibits the release of substance P-like immunoreactivity in the spinal cord of rats following a noxious mechanical stimulus

Abstract

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.