Perspectives in Pharmacology Mechanisms of Induction of Persistent Nociception by Dynorphin

The opioid peptide dynorphin has been demonstrated to be both nociceptive and antinociceptive. This article will review the potential mechanisms through which dynorphin contributes to spinally mediated nociception. Specifically, we will examine the interaction of dynorphin with multiple sites on the NMDA receptor complex. Dynorphin-induced opioid activity is generally inhibitory, with a tendency to impede nociceptive signals and serve in a neuroprotective capacity. In contrast, dynorphin’s interaction with multiple sites on the NMDA receptor complex produces excitatory responses resulting in nociceptive and even toxic effects. Thus, it is hypothesized that dynorphin has both physiological and pathological roles in acute and chronic pain states.