Endogenous dynorphin modulates calcium-mediated antinociception in mice.

We previously reported that calcium administered IT produces antinociception by stimulating spinal Met-enkephalin release. However, at times the antinociceptive effects of calcium in the tail-flick test are greatly diminished. The results of this study indicates that during these periods calcium also stimulates endogenous dynorphin release. Dynorphin has been reported to block opiate-induced antinociception. Calcium-injected mice (150-600 nmol, IT) pretreated with vehicle IP displayed a poor degree of antinociception. Alternatively, pretreating mice with pentobarbital (45 mg/kg, IP) restored the antinociceptive effects of calcium. Low doses of naloxone and norbinaltorphimine (BNI) did not produce antinociception but restored the antinociceptive effects of calcium. Dynorphin (1-17) (Dyn 1-17), and Dyn (1-13), but not Dyn (1-8), blocked the antinociceptive effects of calcium restored with pentobarbital. These results indicate that calcium-mediated antinociception was sensitive to injected dynorphins. In additional experiments, antiserum to Dyn (1-13) was found to restore the antinociceptive effects of calcium, presumably by binding dynorphin released by calcium.